| Description: |
Plumbagin, a potential natural FOXM1 inhibitor, has anticancer, and anti-fibrotic activies, it inactivates the NF-κB/TLR-4 pathway that is associated with inflammatory reactions, thereby mitigating liver fibrosis. Plumbagin offers significant protective role against DEX-induced cellular damage via regulating oxidative stress, apoptosis, and osteogenic markers. |
| Targets: |
Caspase | JNK | P450 (e.g. CYP17) | ROS | p21 | IL Receptor | NF-kB | TLR | TNF-α | FOXM1 |
| In vitro: |
| Cancer Lett. 2015 Feb 1;357(1):265-78. | | Plumbagin induces apoptosis in lymphoma cells via oxidative stress mediated glutathionylation and inhibition of mitogen-activated protein kinase phosphatases (MKP1/2).[Pubmed: 25444924] | Maintaining cellular redox homeostasis is imperative for the survival and normal functioning of cells.
METHODS AND RESULTS:
This study describes the role and regulation of MAPKinases in oxidative stress mediated apoptosis. Plumbagin, a vitamin K3 analog and a pro-oxidant, was employed and it induced apoptosis in both mouse and human T-cell lymphoma cell lines via increased oxidative stress, caspase activity and loss of mitochondrial membrane potential. The pro-oxidant and cytotoxic effects of plumbagin were sensitive to antioxidants indicating a decisive role of cellular redox balance. Plumbagin induced persistent activation of JNK and pharmacological inhibition as well as shRNA-mediated JNK knock-down rescued cells from plumbagin-induced apoptosis. Further, plumbagin induced cytochrome c release, FasL expression and Bax levels via activation of JNK pathway. Exposure of lymphoma cells to plumbagin led to inhibition of total and specific phosphatase activity, increased total protein S-glutathionylation and induced glutathionylation of dual specific phosphatase- 1 and 4 (MKP-1 and MKP-2). The in vivo anti-tumor efficacy of plumbagin was demonstrated using a mouse model.
CONCLUSIONS:
In conclusion, oxidative stress mediated tumor cytotoxicity operates through sustained JNK activation via a novel redox-mediated regulation of MKP-1 and MKP-2. | | Curr Drug Deliv. 2015 Mar 16. | | Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.[Pubmed: 25772029] | Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer.
METHODS AND RESULTS:
Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles.
CONCLUSIONS:
In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer. |
|
| In vivo: |
| Cell Physiol Biochem. 2015;35(4):1599-608. | | Anti-fibrotic effect of plumbagin on CCl₄-lesioned rats.[Pubmed: 25824458] | Our previous studies have shown that plumbagin effectively inhibits hepatic stellate cell (HSC) proliferation. Thus, plumbagin-mediated anti-fibrotic effects in vivo merit further investigation.
METHODS AND RESULTS:
We used rat models to assess the potential benefits of plumbagin against CCl₄-induced liver fibrosis.
The results showed that plumbagin lowered the serum concentrations of liver functional enzymes (ALT, AST, ALB, TBIL) in CCl₄-fibrotic rats while reducing inflammatory cytokine levels (IL-6, TNF-α). As reflected in pathological examinations, rats that were administered plumbagin showed decreased collagen markers (HA, LN, PCIII and CIV) in liver tissues and improved hepatocellular impairments. In addition, plumbagin contributed to down-regulating NF-κB and TLR-4 mRNA in CCl₄-lesioned livers. As revealed in the immunohistochemical assay, plumbagin-administered rats showed reduced levels of α-SMA and TNF-α immunoreactive cells in liver tissue.
CONCLUSIONS:
Collectively, these findings offer appealing evidence that plumbagin may serve as an anti-fibrotic medication through inactivating the NF-κB/TLR-4 pathway that is associated with inflammatory reactions, thereby mitigating liver fibrosis. |
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