Plum, Plumbagin: Click to Expand ⟱
Features:
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naturally occurring naphthoquinone derivative.

–Plumbagin can undergo redox cycling to generate reactive oxygen species (ROS)
-apototosis, activation of caspases, modulation of Bax, Bcl‑2, loss of MMP.
-Cell cycle arrest in cancer cells, often at the G0/G1, or G2/M phases.
-May inhibit NF‑κB activation
– MAPK Pathways
– PI3K/Akt Pathway
-Downregulation of (VEGF) and matrix metalloproteinases (MMPs).

-Seems capable of raising ROS in normal and cancer cells (#2004)

-ic50 cancer cells 1-10uM, normal cells >10uM
Scientific Papers found: Click to Expand⟱
1920- JG,  TQ,  Plum,    Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line
- in-vitro, PC, PANC1
ROS↑, thymoquinone, plumbagin and juglone were evaluated for their influence on reactive oxygen species (ROS) generation through 2,7-dichlorofluorescein diacetate (DCFDA) staining and they dramatically increased the intracellular ROS level in treated PANC-
TumCMig↓, inhibited PANC-1 cell migration
MMP9↓, reduced expression of matrix metalloproteinase-9 (MMP-9) in juglone-treated cells

2004- Plum,    Plumbagin Inhibits Proliferative and Inflammatory Responses of T Cells Independent of ROS Generation But by Modulating Intracellular Thiols
- in-vivo, Var, NA
TumCP↓, Plumbagin inhibited activation, proliferation, cytokine production, and graft-versus-host disease in lymphocytes and inhibited growth of tumor cells
TumCG↓,
NF-kB↓, by suppressing nuclear factor-κB (NF-κB)
ROS↑, Plumbagin was also shown to induce reactive oxygen species (ROS) generation in tumor cells via an unknown mechanism
GSH↓, Plumbagin depleted glutathione (GSH) levels that led to increase in ROS generation
eff↓, production by plumbagin was abrogated by thiol antioxidants but not by non-thiol antioxidants confirming that thiols but not ROS play an important role in biological activity of plumbagin.
i-Thiols↓, Plumbagin depleted intracellular thiols (mainly GSH)
GSH/GSSG↓, plumbagin also induced GSH to GSSG conversion
*GSH↓, In this report, for the first time we show GSH depletion as a source of ROS generation in normal lymphocytes following plumbagin treatment.
*ROS↑, plumbagin-induced increase in ROS levels in lymphocytes

2005- Plum,    Plumbagin induces apoptosis in lymphoma cells via oxidative stress mediated glutathionylation and inhibition of mitogen-activated protein kinase phosphatases (MKP1/2)
- in-vivo, Nor, EL4 - in-vitro, AML, Jurkat
JNK↑, Plumbagin induced persistent activation of JNK
Cyt‑c↑, plumbagin induced cytochrome c release, FasL expression and Bax levels via activation of JNK pathway
FasL↑,
BAX↑,
ROS↑, plumbagin has been reported to induce ROS in normal as well as in tumor cells
*ROS↑, induce ROS in normal as well as in tumor cells
MKP1↓, plumbagin induced oxidative stress may suppress MKP activity in lymphoma cells leading to sustained JNK activation resulting in apoptosis.
MKP2↓,
selectivity∅, Plumbagin induced cell death in EL4(normal) cells and Jurkat cells
tumCV↑, cell viability dramatically decreased with increasing concentrations of plumbagin (0.05-2.5uM) when incubated for 24 or 48 h
Cyt‑c↑, Bax dependent cytochrome c release and apoptosome complex formation is followed by the cleavage of pro-caspase-3
Casp3↑,
GSH/GSSG↓, progressive decrease in GSH/GSSG ratio in tumor cells following plumbagin treatment
ROS↑, simultaneous increase in the levels of intracellular ROS was observed in both these cell lines which remained high up to 4 h indicating an increase in oxidative stress in tumor cells
mt-ROS↑, While we observed low basal mtROS levels in untreated cells, plumbagin treatment resulted in a significant increase in mtROS levels
*ROS↑, both cell lines, meaning normal EL4 cells too
eff↓, NAC, GSH and PEG-catalase were able to abrogate plumbagin induced ROS and cell death.

2006- Plum,    Plumbagin induces apoptosis in human osteosarcoma through ROS generation, endoplasmic reticulum stress and mitochondrial apoptosis pathway
- in-vitro, OS, MG63 - in-vitro, Nor, hFOB1.19
tumCV↓, Plumbagin reduced cell viability in osteosarcoma cells but not normal bone cells
selectivity↑,
mtDam↑, Plumbagin induced cell apoptosis by mitochondrial dysfunction, which in turn promoted Ca2+ release and endoplasmic reticulum (ER)‑stress
Ca+2↓,
ER Stress↑,
ROS↑, plumbagin improved reactive oxygen species (ROS) generation
Casp3↑, apoptotic cascades activated caspase‑3 and caspase‑9 to elicit apoptosis response
Casp9↑,
Apoptosis↑,
eff↓, Moreover, plumbagin-induced apoptosis was reversed by pretreating with ROS scavenger N-acetyl cysteine (NAC), NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and H2O2 scavenging enzyme (catalase)

2651- Plum,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, Various studies have shown that plumbagin is a potent inducer of ROS
TrxR↓, The mechanism underlying ROS induction by plumbagin has predominantly been attributed to inhibition of the antioxidant enzymes TrxR
GSR↓, and glutathione reductase
ER Stress↓, mediates its anticancer effect by inducing ER stress-mediated apoptosis
TumCCA↑, S/G2 and G2/M cell cycle arrest
MMP↓, and mitochondrial membrane depolarization in an ROS-dependent manner
NF-kB↓, plumbagin was found to inhibit the NF-κB [57], PI3K/AKT/mTOR [58] and MKP1/2 [59] pathways in non-small cell lung cancer, bladder cancer, and lymphoma,
PI3K↓,
Akt↓,
mTOR↓,
MKP1↓,
MKP2↓,
ChemoSen↑, improve the efficacy of existing chemotherapeutic strategies


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Apoptosis↑,1,   BAX↑,1,   Ca+2↓,1,   Casp3↑,2,   Casp9↑,1,   ChemoSen↑,1,   Cyt‑c↑,2,   eff↓,3,   ER Stress↓,1,   ER Stress↑,1,   FasL↑,1,   GSH↓,1,   GSH/GSSG↓,2,   GSR↓,1,   JNK↑,1,   MKP1↓,2,   MKP2↓,2,   MMP↓,1,   MMP9↓,1,   mtDam↑,1,   mTOR↓,1,   NF-kB↓,2,   PI3K↓,1,   ROS↑,6,   mt-ROS↑,1,   selectivity↑,1,   selectivity∅,1,   i-Thiols↓,1,   TrxR↓,1,   TumCCA↑,1,   TumCG↓,1,   TumCMig↓,1,   TumCP↓,1,   tumCV↓,1,   tumCV↑,1,  
Total Targets: 36

Results for Effect on Normal Cells:
GSH↓,1,   ROS↑,3,  
Total Targets: 2

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