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| 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 half-life 30–60 minutes BioAv poor aqueous solubility and bioavailability Pathways: - induce ROS production in cancer cells likely at any dose. Effect on normal cells is inconclusive. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, Prx, - Lowers some AntiOxidant markers/ defense in Cancer Cells: but mostly raises NRF2 (raises antiO defense), TrxR↓(*important), GSH↓ Catalase↓ HO1↓ GPx↓ - Very little indication of raising AntiOxidant defense in Normal Cells: GSH↑, - lowers Inflammation : NF-kB↓, COX2↓, conversely p38↑, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, VEGF↓, NF-κB↓, CXCR4↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓(few reports), DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, - small indication of inhibiting glycolysis : HIF-1α↓, cMyc↓, LDH↓, HK2↓, - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, ERK↓, JNK, - Synergies: chemo-sensitization, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells
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| In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+. Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors. In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2). Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways. Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer. Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation. High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses. Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes. |
| 1939- | PL, | Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP |
| - | in-vitro, | HCC, | HepG2 | - | in-vitro, | HCC, | HUH7 | - | in-vivo, | NA, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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