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PL Piperlongumine

Description: Piperlongumine (also called Piplartine), an alkaloid from long pepper fruit 
-Piperlongumine is a bioactive alkaloid derived from the long pepper (Piper longum) 
– Piperlongumine has been shown to selectively increase ROS levels in cancer cells. 
-NLRP3 inhibitor? 
-TrxR inhibitor (major antioxidant system) to increase ROS in cancer cells 
-ic50 cancer cells maybe 2-10uM, normal cells maybe exceeding 20uM. 
 
Available from mcsformulas.com 
-(Long Pepper, 500mg/Capsule)- 1 capsule 3 times daily with food 
-Piperlongumine Pro Liposomal, 40 mg-take 1 capsule daily with plenty of water, after a meal 

 
-Note <a href="tbResList.php?qv=134&tsv=1109&wNotes=on&exSp=open">half-life</a> 30–60 minutes 
<a href="tbResList.php?qv=134&tsv=792&wNotes=on&exSp=open">BioAv</a> poor aqueous solubility and bioavailability
 
Pathways: 


- induce
<a href="tbResList.php?qv=134&tsv=275&wNotes=on">ROS</a> production in cancer cells likely at any dose. Effect on normal cells is inconclusive. 
- ROS↑ related:
<a href="tbResList.php?qv=134&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?qv=134&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?qv=134&tsv=459&wNotes=on">UPR↑</a>,


<a href="tbResList.php?qv=134&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?qv=134&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?qv=134&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?qv=134&tsv=239&wNotes=on">cl-PARP↑</a>,

<a href="tbResList.php?qv=134&wNotes=on&word=Prx">Prx</a>,

 


- Lowers some AntiOxidant markers/ defense in Cancer Cells:
<a href="tbResList.php?qv=134&tsv=226&wNotes=on&word=NRF2"> but mostly raises NRF2 </a>(raises antiO defense),
<a href="tbResList.php?qv=134&word=Trx&wNotes=on">TrxR↓</a>(*important),

<a href="tbResList.php?qv=134&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<a href="tbResList.php?qv=134&tsv=46&wNotes=on">Catalase↓</a>
<a href="tbResList.php?qv=134&tsv=597&wNotes=on">HO1↓</a>
<a href="tbResList.php?qv=134&wNotes=on&word=GPx">GPx↓</a>
 

- Very little indication of raising
<a href="tbResList.php?qv=134&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:



<a href="tbResList.php?qv=134&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,

 


- lowers
<a href="tbResList.php?qv=134&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?qv=134&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?qv=134&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?qv=134&tsv=235&wNotes=on&word=p38">conversely p38↑</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?qv=134&tsv=908&wNotes=on&word=NLRP3↓">NLRP3↓</a>,
<a href="tbResList.php?qv=134&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?qv=134&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?qv=134&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?qv=134&tsv=368&wNotes=on&word=IL8↓">IL-8↓</a>
 


- inhibit Growth/Metastases :
<a href="tbResList.php?qv=134&tsv=604&wNotes=on">TumMeta↓</a>,
<a href="tbResList.php?qv=134&tsv=323&wNotes=on">TumCG↓</a>,
<a href="tbResList.php?qv=134&tsv=96&wNotes=on">EMT↓</a>,

<a href="tbResList.php?qv=134&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?qv=134&tsv=203&wNotes=on">MMP9↓</a>,



<a href="tbResList.php?qv=134&tsv=334&wNotes=on">VEGF↓</a>,



<a href="tbResList.php?qv=134&tsv=214&wNotes=on">NF-κB↓</a>,
<a href="tbResList.php?qv=134&tsv=79&wNotes=on">CXCR4↓</a>,



<a href="tbResList.php?qv=134&tsv=105&wNotes=on">ERK↓</a>
 


- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=134&tsv=140&wNotes=on">HDAC↓</a>(few reports),
<a href="tbResList.php?qv=134&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=134&tsv=86&wNotes=on">DNMT3A↓</a>,
<a href="tbResList.php?qv=134&tsv=108&wNotes=on">EZH2↓</a>,
<a href="tbResList.php?qv=134&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?qv=134&wNotes=on&word=HSP">HSP↓</a>,
<a href="tbResList.php?qv=134&tsv=506&wNotes=on">Sp proteins↓</a>,
 


- cause Cell cycle arrest :
<a href="tbResList.php?qv=134&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?qv=134&tsv=73&wNotes=on">cyclin D1↓</a>,

<a href="tbResList.php?qv=134&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?qv=134&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?qv=134&tsv=895&wNotes=on">CDK6↓</a>,
 


- inhibits Migration/Invasion :
<a href="tbResList.php?qv=134&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?qv=134&tsv=324&wNotes=on">TumCI↓</a>,

<a href="tbResList.php?qv=134&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=134&tsv=96&wNotes=on">EMT↓</a>,


 


- small indication of inhibiting
<a href="tbResList.php?qv=134&tsv=129&wNotes=on">glycolysis</a>
:
<a href="tbResList.php?qv=134&tsv=143&wNotes=on">HIF-1α↓</a>,

<a href="tbResList.php?qv=134&tsv=35&wNotes=on">cMyc↓</a>,

<a href="tbResList.php?qv=134&tsv=906&wNotes=on">LDH↓</a>,

<a href="tbResList.php?qv=134&tsv=773&wNotes=on">HK2↓</a>,

 


- inhibits
<a href="tbResList.php?qv=134&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=134&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=134&tsv=143&wNotes=on">HIF-1α↓</a>,



<a href="tbResList.php?qv=134&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,

 




- Others: <a href="tbResList.php?qv=134&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=134&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=134&wNotes=on&word=JAK">JAK↓</a>,
<a href="tbResList.php?qv=134&wNotes=on&word=STAT">STAT↓</a>,

<a href="tbResList.php?qv=134&tsv=342&wNotes=on">β-catenin↓</a>,


<a href="tbResList.php?qv=134&tsv=105&wNotes=on">ERK↓</a>,

<a href="tbResList.php?qv=134&tsv=168&wNotes=on">JNK</a>,

 


- Synergies:
<a href="tbResList.php?qv=134&tsv=1106&wNotes=on">chemo-sensitization</a>,

<a href="tbResList.php?qv=134&tsv=1107&wNotes=on">RadioSensitizer</a>,

<a href="tbResList.php?qv=134&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=134&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=134&tsv=557&wNotes=on">Cognitive</a>,

<a href="tbResList.php?qv=134&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=134&tsv=1188&wNotes=on">CardioProtective</a>,

 
 

- Selectivity:
<a href="tbResList.php?qv=134&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
 

<table>
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>

<tr>
<td>1</td>
<td>Transformation-linked oxidative stress dependence</td>
<td>↑ ROS</td>
<td>Cancer-selective stress overload</td>
<td>Landmark study: piperlongumine selectively kills cells with a cancer genotype by elevating ROS; antioxidant rescue blocks killing</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21753854/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>GSTP1 redox buffering (glutathione S-transferase π)</td>
<td>↓ GSTP1 function / ↑ ROS</td>
<td>Disables antioxidant buffering</td>
<td>Biochemical/structural work describing GSTP1 as a piperlongumine target and linking PL exposure to increased ROS and decreased GSH</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5217671/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>ER stress / UPR via PRDX4 (Peroxiredoxin 4)</td>
<td>↓ PRDX4 activity / ↑ ER stress</td>
<td>Proteotoxic stress, preferential glioma killing</td>
<td>Piperlongumine inactivates PRDX4, exacerbates ER stress, increases ROS, and preferentially kills high-grade glioma cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24879047/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>Mitochondrial disruption + stress MAPK (JNK)</td>
<td>↓ ΔΨm / ↑ JNK</td>
<td>Mitochondrial apoptosis signaling</td>
<td>Example mechanistic paper: piperlongumine induces ROS-mediated mitochondrial disruption and activates JNK associated with apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/29543494/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>DNA damage response</td>
<td>↑ DNA damage</td>
<td>Checkpoint activation, death signaling</td>
<td>Piperlongumine elevates ROS and causes DNA damage in pancreatic cancer models; antioxidant reverses DNA damage and killing</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/25530945/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>STAT3 signaling</td>
<td>↓ STAT3 activity (↓ pSTAT3 / ↓ STAT3 function)</td>
<td>Reduced survival & stem-like growth</td>
<td>Drug-repositioning study identifies piperlongumine as a direct STAT3 inhibitor; shows reduced STAT3 activation and mammosphere inhibition</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24681959/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB DNA binding / ↓ nuclear translocation</td>
<td>Reduced inflammatory & anti-apoptotic transcription</td>
<td>Piperlongumine down-regulates NF-κB DNA-binding activity and decreases nuclear translocation of p50/p65 in prostate cancer cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24151226/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>PI3K–AKT–mTOR pathway</td>
<td>↓ PI3K/AKT/mTOR signaling</td>
<td>Growth suppression; promotes apoptosis/autophagy</td>
<td>Paper explicitly reporting piperlongumine induces apoptosis and autophagy through inhibition of PI3K/Akt/mTOR in lung cancer cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/26246196/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>p38 signaling (stress kinase)</td>
<td>↑ p38 signaling</td>
<td>Stress response; autophagy involvement</td>
<td>Mechanistic study showing piperlongumine induces autophagy by targeting p38 signaling</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/24091667/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>Cell cycle regulation</td>
<td>↑ G2/M arrest</td>
<td>Proliferation block</td>
<td>Demonstrates piperlongumine induces G2/M cell-cycle arrest in MCF-7 cells (cell cycle distribution shift shown)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/31739520/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>EMT / migration / invasion</td>
<td>↓ EMT / ↓ migration & invasion</td>
<td>Anti-metastatic phenotype</td>
<td>Reports piperlongumine inhibits TGF-β–induced EMT and reduces migration/invasion in cancer cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/28734931/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>Ferroptosis (iron-dependent oxidative death)</td>
<td>↑ ferroptosis</td>
<td>Non-apoptotic killing modality</td>
<td>Shows piperlongumine-induced cancer cell death is inhibited by ferroptosis inhibitors and iron chelation, supporting ferroptosis involvement</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/29393418/" target="_blank">(ref)</a></td>
</tr>

</table>

Research papers

Year	Title	Authors	PMID	Link
2025	Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover	Ruirui Wang	—	https://pmc.ncbi.nlm.nih.gov/articles/PMC11949057/
2025	Piperlongumine induces ROS accumulation to reverse resistance of 5-FU in human colorectal cancer via targeting TrxR	Ji Zhou	40054719	https://pubmed.ncbi.nlm.nih.gov/40054719/
2024	Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1	Priya Singh	38091824	https://pubmed.ncbi.nlm.nih.gov/38091824/
2024	Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells	Fatemeh Jamali	—	https://www.mdpi.com/2076-3921/13/10/1201
2024	Piperlongumine inhibits antioxidant enzymes, increases ROS levels, induces DNA damage and G2/M cell cycle arrest in breast cell lines	Adrivanio Baranoski	38279841	https://pubmed.ncbi.nlm.nih.gov/38279841/
2024	The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy	Yu Tang	—	https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1280779/full
2024	Piperlongumine and its derivatives against cancer: A recent update and future prospective	Shasank S. Swain	—	https://onlinelibrary.wiley.com/doi/10.1002/ardp.202300768?af=R
2024	Piperlongumine inhibits esophageal squamous cell carcinoma in vitro and in vivo by triggering NRF2/ROS/TXNIP/NLRP3-dependent pyroptosis	Yue Cui	—	https://www.sciencedirect.com/science/article/abs/pii/S0009279724000218
2023	Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer	Shatakshi Mitra	—	https://link.springer.com/article/10.1007/s00210-023-02673-5
2023	Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence	Zohra Nausheen Nizami	PMC10295724	https://pmc.ncbi.nlm.nih.gov/articles/PMC10295724/
2023	Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy	Menglu Wang	36493999	https://pubmed.ncbi.nlm.nih.gov/36493999/
2023	A strategy to improve the solubility and bioavailability of the insoluble drug piperlongumine through albumin nanoparticles	Sen Niu	—	https://www.pjps.pk/uploads/2023/03/1679394499.pdf
2022	Piperlongumine mitigates LPS-induced inflammation and lung injury via targeting MD2/TLR4	Yelin Tang	—	https://www.researchgate.net/publication/366043142_Piperlongumine_mitigates_LPS-induced_inflammation_and_lung_injury_via_targeting_MD2TLR4
2022	Natural product piperlongumine inhibits proliferation of oral squamous carcinoma cells by inducing ferroptosis and inhibiting intracellular antioxidant capacity	Zi-Qian Wang	PMC10643964	https://pmc.ncbi.nlm.nih.gov/articles/PMC10643964/
2022	Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity	Jie Shi	PMC8790537	https://pmc.ncbi.nlm.nih.gov/articles/PMC8790537/
2022	Piperlongumine alleviates corneal allograft rejection via suppressing angiogenesis and inflammation	Xiangyu Fan	—	https://pmc.ncbi.nlm.nih.gov/articles/PMC9802119/
2022	Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin	Yijia Yang	PMC9030593	https://pmc.ncbi.nlm.nih.gov/articles/PMC9030593/
2021	Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation	Ai-Ling Sun	PMC8198376	https://pmc.ncbi.nlm.nih.gov/articles/PMC8198376/
2021	The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells	Leanne M Delaney	33019824	https://pubmed.ncbi.nlm.nih.gov/33019824/
2021	Overview of piperlongumine analogues and their therapeutic potential	Peng Zhu	—	https://www.sciencedirect.com/science/article/abs/pii/S0223523421003202
2021	Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells	Fang-Ping Kung	PMC8428232	https://pmc.ncbi.nlm.nih.gov/articles/PMC8428232/
2021	The promising potential of piperlongumine as an emerging therapeutics for cancer	Dey Parama	—	https://www.explorationpub.com/uploads/Article/A100249/100249.pdf
2020	Application of longinamide in inhibiting the activation of NLRP3 inflammasome		—	https://patents.google.com/patent/CN114073693A/en
2020	Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation	Jie Liang	PMC7303365	https://pmc.ncbi.nlm.nih.gov/articles/PMC7303365/
2020	Biological and physical approaches on the role of piplartine (piperlongumine) in cancer	Tiago Henrique	—	https://www.nature.com/articles/s41598-020-78220-6
2020	Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells	Laxminarayan Rawat	—	https://www.sciencedirect.com/science/article/pii/S0753332220304352
2020	Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation	Sowjanya Thatikonda	PMC6954241	https://pmc.ncbi.nlm.nih.gov/articles/PMC6954241/
2020	The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer	Marta Hałas-Wiśniewska	PMC7411589	https://pmc.ncbi.nlm.nih.gov/articles/PMC7411589/
2020	Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling	Peng Zhu	33026807	https://pubmed.ncbi.nlm.nih.gov/33026807/
2020	Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor	Qing-Zhu Fan	33113415	https://pubmed.ncbi.nlm.nih.gov/33113415/
2020	Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent	Surya Kant Tripath	—	https://www.sciencedirect.com/science/article/abs/pii/S1043661820307830
2019	Piperlongumine Induces Reactive Oxygen Species (ROS)-dependent Downregulation of Specificity Protein Transcription Factors	Keshav Karki	PMC6357769	https://pmc.ncbi.nlm.nih.gov/articles/PMC6357769/
2019	Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress	Qianqian Zhang	PMC6802400	https://pmc.ncbi.nlm.nih.gov/articles/PMC6802400/
2019	Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems	Hui Wang	30790679	https://pubmed.ncbi.nlm.nih.gov/30790679/
2019	Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells	Jin-Ah Park	PMC6939652	https://pmc.ncbi.nlm.nih.gov/articles/PMC6939652/
2019	Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKβ Suppression in Human Breast Cancer Cells	Chang Hee Jeong	—	https://www.researchgate.net/publication/337268185_Piperlongumine_Induces_Cell_Cycle_Arrest_via_Reactive_Oxygen_Species_Accumulation_and_IKKb_Suppression_in_Human_Breast_Cancer_Cells
2018	Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis	Yuki Yamaguchi	—	https://www.researchgate.net/publication/322834071_Piperlongumine_rapidly_induces_the_death_of_human_pancreatic_cancer_cells_mainly_through_the_induction_of_ferroptosis
2018	Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease	Jun Go	—	https://www.sciencedirect.com/science/article/abs/pii/S1756464618300471
2017	Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization	Di Liu	—	https://www.sciencedirect.com/science/article/abs/pii/S0006291X17320399
2017	Piperlongumine attenuates IL-1β-induced inflammatory response in chondrocytes	Yifeng Hu	—	https://www.alliedacademies.org/articles/piperlongumine-attenuates-il1betainduced-inflammatory-response-in-chondrocytes-9907.html
2017	Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways	Hongfei Wang	PMC5774427	https://pmc.ncbi.nlm.nih.gov/articles/PMC5774427/
2016	Preformulation Studies on Piperlongumine	Alhassan Aodah	—	https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151707
2016	Piperlongumine for enhancing oral bioavailability and cytotoxicity of docetaxel in triple negative breast cancer	Ketan Patel	—	https://pmc.ncbi.nlm.nih.gov/articles/PMC4706797/
2016	Preparation of piperlongumine-loaded chitosan nanoparticles for safe and efficient cancer therapy	Jayachandran Venkatesan	—	https://www.researchgate.net/publication/306126947_Preparation_of_piperlongumine-loaded_chitosan_nanoparticles_for_safe_and_efficient_cancer_therapy
2016	Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer	Peng Zou	26963494	https://pubmed.ncbi.nlm.nih.gov/26963494/
2016	Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation	Wen-Jing Yan	27233942	https://pubmed.ncbi.nlm.nih.gov/27233942/
2015	Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2‑Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents	Jianguo Fang	—	https://www.academia.edu/21621417/Synthesis_of_Piperlongumine_Analogues_and_Discovery_of_Nuclear_Factor_Erythroid_2_Related_Factor_2_Nrf2_Activators_as_Potential_Neuroprotective_Agents
2015	Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine	Ha-Na Lee	PMC4400307	https://pmc.ncbi.nlm.nih.gov/articles/PMC4400307/
2015	Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents	Shoujiao Peng	—	https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00410
2015	Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP	Yong Chen	PMC4467445	https://pmc.ncbi.nlm.nih.gov/articles/PMC4467445/
2014	Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells	Tae Hyong Kim	PMC4165421	https://pmc.ncbi.nlm.nih.gov/articles/PMC4165421/
2014	Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer	Jong-Lyel Roh	PMC4253430	https://pmc.ncbi.nlm.nih.gov/articles/PMC4253430/
2014	Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways	Qian Rong Liu	PMC4055624	https://pmc.ncbi.nlm.nih.gov/articles/PMC4055624/
2013	Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation	Ju Mei Liu	—	https://www.sciencedirect.com/science/article/abs/pii/S0006291X13010292
2013	Piperlongumine induces autophagy by targeting p38 signaling	Y Wang	—	https://www.nature.com/articles/cddis2013358
2011	Selective killing of cancer cells by a small molecule targeting the stress response to ROS	Lakshmi Raj	—	https://www.nature.com/articles/nature10167

Year

Title

Authors

PMID

Link

Flag

2025

Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover

Ruirui Wang

—

https://pmc.ncbi.nlm.nih.gov/articles/PMC11949057/

2025

Piperlongumine induces ROS accumulation to reverse resistance of 5-FU in human colorectal cancer via targeting TrxR

Ji Zhou

40054719

https://pubmed.ncbi.nlm.nih.gov/40054719/

2024

Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1

Priya Singh

38091824

https://pubmed.ncbi.nlm.nih.gov/38091824/

2024

Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells

Fatemeh Jamali

—

https://www.mdpi.com/2076-3921/13/10/1201

2024

Piperlongumine inhibits antioxidant enzymes, increases ROS levels, induces DNA damage and G2/M cell cycle arrest in breast cell lines

Adrivanio Baranoski

38279841

https://pubmed.ncbi.nlm.nih.gov/38279841/

2024

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy

Yu Tang

—

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1280779/full

2024

Piperlongumine and its derivatives against cancer: A recent update and future prospective

Shasank S. Swain

—

https://onlinelibrary.wiley.com/doi/10.1002/ardp.202300768?af=R

2024

Piperlongumine inhibits esophageal squamous cell carcinoma in vitro and in vivo by triggering NRF2/ROS/TXNIP/NLRP3-dependent pyroptosis

Yue Cui

—

https://www.sciencedirect.com/science/article/abs/pii/S0009279724000218

2023

Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer

Shatakshi Mitra

—

https://link.springer.com/article/10.1007/s00210-023-02673-5

2023

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Zohra Nausheen Nizami

PMC10295724

https://pmc.ncbi.nlm.nih.gov/articles/PMC10295724/

2023

Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy

Menglu Wang

36493999

https://pubmed.ncbi.nlm.nih.gov/36493999/

2023

A strategy to improve the solubility and bioavailability of the insoluble drug piperlongumine through albumin nanoparticles

Sen Niu

—

https://www.pjps.pk/uploads/2023/03/1679394499.pdf

2022

Piperlongumine mitigates LPS-induced inflammation and lung injury via targeting MD2/TLR4

Yelin Tang

—

https://www.researchgate.net/publication/366043142_Piperlongumine_mitigates_LPS-induced_inflammation_and_lung_injury_via_targeting_MD2TLR4

2022

Natural product piperlongumine inhibits proliferation of oral squamous carcinoma cells by inducing ferroptosis and inhibiting intracellular antioxidant capacity

Zi-Qian Wang

PMC10643964

https://pmc.ncbi.nlm.nih.gov/articles/PMC10643964/

2022

Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity

Jie Shi

PMC8790537

https://pmc.ncbi.nlm.nih.gov/articles/PMC8790537/

2022

Piperlongumine alleviates corneal allograft rejection via suppressing angiogenesis and inflammation

Xiangyu Fan

—

https://pmc.ncbi.nlm.nih.gov/articles/PMC9802119/

2022

Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin

Yijia Yang

PMC9030593

https://pmc.ncbi.nlm.nih.gov/articles/PMC9030593/

2021

Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation

Ai-Ling Sun

PMC8198376

https://pmc.ncbi.nlm.nih.gov/articles/PMC8198376/

2021

The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells

Leanne M Delaney

33019824

https://pubmed.ncbi.nlm.nih.gov/33019824/

2021

Overview of piperlongumine analogues and their therapeutic potential

Peng Zhu

—

https://www.sciencedirect.com/science/article/abs/pii/S0223523421003202

2021

Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells

Fang-Ping Kung

PMC8428232

https://pmc.ncbi.nlm.nih.gov/articles/PMC8428232/

2021

The promising potential of piperlongumine as an emerging therapeutics for cancer

Dey Parama

—

https://www.explorationpub.com/uploads/Article/A100249/100249.pdf

2020

Application of longinamide in inhibiting the activation of NLRP3 inflammasome

—

https://patents.google.com/patent/CN114073693A/en

2020

Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation

Jie Liang

PMC7303365

https://pmc.ncbi.nlm.nih.gov/articles/PMC7303365/

2020

Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

Tiago Henrique

—

https://www.nature.com/articles/s41598-020-78220-6

2020

Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells

Laxminarayan Rawat

—

https://www.sciencedirect.com/science/article/pii/S0753332220304352

2020

Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation

Sowjanya Thatikonda

PMC6954241

https://pmc.ncbi.nlm.nih.gov/articles/PMC6954241/

2020

The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer

Marta Hałas-Wiśniewska

PMC7411589

https://pmc.ncbi.nlm.nih.gov/articles/PMC7411589/

2020

Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling

Peng Zhu

33026807

https://pubmed.ncbi.nlm.nih.gov/33026807/

2020

Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor

Qing-Zhu Fan

33113415

https://pubmed.ncbi.nlm.nih.gov/33113415/

2020

Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent

Surya Kant Tripath

—

https://www.sciencedirect.com/science/article/abs/pii/S1043661820307830

2019

Piperlongumine Induces Reactive Oxygen Species (ROS)-dependent Downregulation of Specificity Protein Transcription Factors

Keshav Karki

PMC6357769

https://pmc.ncbi.nlm.nih.gov/articles/PMC6357769/

2019

Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress

Qianqian Zhang

PMC6802400

https://pmc.ncbi.nlm.nih.gov/articles/PMC6802400/

2019

Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems

Hui Wang

30790679

https://pubmed.ncbi.nlm.nih.gov/30790679/

2019

Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells

Jin-Ah Park

PMC6939652

https://pmc.ncbi.nlm.nih.gov/articles/PMC6939652/

2019

Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKβ Suppression in Human Breast Cancer Cells

Chang Hee Jeong

—

https://www.researchgate.net/publication/337268185_Piperlongumine_Induces_Cell_Cycle_Arrest_via_Reactive_Oxygen_Species_Accumulation_and_IKKb_Suppression_in_Human_Breast_Cancer_Cells

2018

Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis

Yuki Yamaguchi

—

https://www.researchgate.net/publication/322834071_Piperlongumine_rapidly_induces_the_death_of_human_pancreatic_cancer_cells_mainly_through_the_induction_of_ferroptosis

2018

Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

Jun Go

—

https://www.sciencedirect.com/science/article/abs/pii/S1756464618300471

2017

Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization

Di Liu

—

https://www.sciencedirect.com/science/article/abs/pii/S0006291X17320399

2017

Piperlongumine attenuates IL-1β-induced inflammatory response in chondrocytes

Yifeng Hu

—

https://www.alliedacademies.org/articles/piperlongumine-attenuates-il1betainduced-inflammatory-response-in-chondrocytes-9907.html

2017

Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways

Hongfei Wang

PMC5774427

https://pmc.ncbi.nlm.nih.gov/articles/PMC5774427/

2016

Preformulation Studies on Piperlongumine

Alhassan Aodah

—

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151707

2016

Piperlongumine for enhancing oral bioavailability and cytotoxicity of docetaxel in triple negative breast cancer

Ketan Patel

—

https://pmc.ncbi.nlm.nih.gov/articles/PMC4706797/

2016

Preparation of piperlongumine-loaded chitosan nanoparticles for safe and efficient cancer therapy

Jayachandran Venkatesan

—

https://www.researchgate.net/publication/306126947_Preparation_of_piperlongumine-loaded_chitosan_nanoparticles_for_safe_and_efficient_cancer_therapy

2016

Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer

Peng Zou

26963494

https://pubmed.ncbi.nlm.nih.gov/26963494/

2016

Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation

Wen-Jing Yan

27233942

https://pubmed.ncbi.nlm.nih.gov/27233942/

2015

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2‑Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

Jianguo Fang

—

https://www.academia.edu/21621417/Synthesis_of_Piperlongumine_Analogues_and_Discovery_of_Nuclear_Factor_Erythroid_2_Related_Factor_2_Nrf2_Activators_as_Potential_Neuroprotective_Agents

2015

Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine

Ha-Na Lee

PMC4400307

https://pmc.ncbi.nlm.nih.gov/articles/PMC4400307/

2015

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

Shoujiao Peng

—

https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00410

2015

Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP

Yong Chen

PMC4467445

https://pmc.ncbi.nlm.nih.gov/articles/PMC4467445/

2014

Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells

Tae Hyong Kim

PMC4165421

https://pmc.ncbi.nlm.nih.gov/articles/PMC4165421/

2014

Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

Jong-Lyel Roh

PMC4253430

https://pmc.ncbi.nlm.nih.gov/articles/PMC4253430/

2014

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Qian Rong Liu

PMC4055624

https://pmc.ncbi.nlm.nih.gov/articles/PMC4055624/

2013

Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation

Ju Mei Liu

—

https://www.sciencedirect.com/science/article/abs/pii/S0006291X13010292

2013

Piperlongumine induces autophagy by targeting p38 signaling

Y Wang

—

https://www.nature.com/articles/cddis2013358

2011

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Lakshmi Raj

—

https://www.nature.com/articles/nature10167

tbResList Print — PL Piperlongumine

Product

Pathway results for Effect on Cancer / Diseased Cells

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Research papers