Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo

Abstract

Angiogenesis is a hallmark of tumor development and metastatic progression, and antiangiogenic drugs targeting the VEGF pathway have shown to decrease the disease progression in cancer patients. In this study, we have analyzed the anti-proliferative and anti-angiogenic property of plumbagin in cisplatin sensitive, BRCA2 deficient, PEO-1 and cisplatin resistant, BRCA2 proficient PEO-4 ovarian cancer cells. Both PEO-1 and PEO-4 ovarian cancer cells are sensitive to plumbagin irrespective of BRCA2 status in both normoxia and hypoxia. Importantly, plumbagin treatment effectively inhibits VEGF-A and Glut-1 in PEO-1 and PEO-4 ovarian cancer cells. We have also analyzed the p53 mutant, cisplatin resistant, and BRCA2 proficient OVCAR-5 cells. Plumbagin challenge also restricts the VEGF induced pro-angiogenenic signaling in HUVECs and subsequently endothelial cell proliferation. In addition, we observe a significant effect on tumor regression among OVCAR-5 tumor-bearing mice treated with plumbagin, which is associated with significant inhibition of Ki67 and vWF expressions. Plumbagin also significantly reduces CD31 expression in an ear angiogenesis assay. Collectively, our studies indicate that plumbagin, as an anti-cancer agent disrupts growth of ovarian cancer cells through the inhibition of proliferation as well as angiogenesis.

Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi-1 cells through upregulation of TRAIL death receptor expression, activation of caspase-8 and inhibition of cFLIP

“…induces apoptosis and exerts anti-proliferation activity in diverse cancer cell lines, such as leukemia (19,20), lung cancer (21,22), prostate cancer (23), breast cancer (24)(25)(26), ovarian cancer (27), cervical cancer (28) and melanoma (29). The mechanisms of its antitumor effect are still not fully unveiled.…”

Histo-Chromatographic Finger Printing Profiles of the Root of Plumbago zeylanica Linn and Quantification of Marker Compound, Plumbagin

“…ROS molecules like superoxide, hydroxyl radical, and hydrogen peroxide cause oxidative damage to protein, DNA and phospholipids. 5,6 Thus having the properties of being a reactive oxygen species (ROS) generator and apoptosis inducing agent, plumbagin has recently been implicated with altering multiple cancer -signaling pathways and reported to have shown immense potentials in anticancer (such as breast, prostrate, ovarian, lung, liver, pancreatic, renal, cervical and skin cancer, also in myeloma and leukemia) [7][8][9][10][11][12][13][14] therapy and in radiation therapy as the chemosensitizer and radiosensitizer. [15][16][17] Genus Plumbago(Plum-Bay-go)of the family Plumbaginaceae is comprised of about 17 species.…”

Plant-derived anticancer agents: a promising treatment for bone metastasis

“…The properties are exerted through a variety of mechanisms, including signal transducer and activator of transcription 3 (STAT3) activation, 15 induction of p53 and c-Jun N-terminal kinase expression in human nonsmall-cell lung cancer cells, 16 inhibition of the nuclear factor-kB (NF-kB)/Bcl-2 pathway 12 and by downregulating the expression of the chemokine receptor CXCR4. 17 The antitumor effects of plumbagin have been shown in several cancers including squamous cell carcinoma, 18 leukemia 19 and myeloma, 15 as well as breast, 17,20 ovarian, 21 pancreatic, 22 lung, 23 liver 24 and cervical cancers. 25 In bone, breast cancer cells increase bone resorption by producing factors such as the parathyroid hormone-related protein (PTHrP) and interleukins that stimulate the osteoblasts and increase the production of the receptor activator of NF-kB (RANK) ligand (RANKL).…”