Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells
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AbstractPlumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer. 2014 Bentham Science Publishers.
CitationSagar S, Esau L, Moosa B, Khashab N, Bajic V, et al. (2014) Cytotoxicity and Apoptosis Induced by a Plumbagin Derivative in Estrogen Positive MCF-7 Breast Cancer Cells. Anti-Cancer Agents in Medicinal Chemistry 14: 170-180. doi:10.2174/18715206113136660369.
PublisherBentham Science Publishers Ltd.
PubMed Central IDPMC3894702
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Except where otherwise noted, this item's license is described as This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
- The natural anticancer agent plumbagin induces potent cytotoxicity in MCF-7 human breast cancer cells by inhibiting a PI-5 kinase for ROS generation.
- Authors: Lee JH, Yeon JH, Kim H, Roh W, Chae J, Park HO, Kim DM
- Issue date: 2012
- The role of thioredoxin reductase and glutathione reductase in plumbagin-induced, reactive oxygen species-mediated apoptosis in cancer cell lines.
- Authors: Hwang GH, Ryu JM, Jeon YJ, Choi J, Han HJ, Lee YM, Lee S, Bae JS, Jung JW, Chang W, Kim LK, Jee JG, Lee MY
- Issue date: 2015 Oct 15
- Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-kappaB and Bcl-2.
- Authors: Ahmad A, Banerjee S, Wang Z, Kong D, Sarkar FH
- Issue date: 2008 Dec 15
- Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo.
- Authors: Hsu YL, Cho CY, Kuo PL, Huang YT, Lin CC
- Issue date: 2006 Aug
- Structure activity relationship of plumbagin in BRCA1 related cancer cells.
- Authors: K A T, T R, G R, K C S, Nair RS, G S, Banerji A, Somasundaram V, Srinivas P
- Issue date: 2013 May
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