Nutraceuticals and Cancer by Fazlul H. H. Sarkar

Author:Fazlul H. H. Sarkar
Language: eng
Format: epub
Publisher: Springer Netherlands, Dordrecht

10.4.7 Other Cancers

In a study to evaluate the differential ability of selected compounds to inhibit cell growth in relation to BRCA1 (breast cancer 1, early onset) status in ER-positive ovarian cancer cells (Thasni et al. 2008), plumbagin was found to be the most effective inducer of apoptosis through its binding to and modulation of ER-alpha in BRCA1 silenced cells. In an earlier study, the effect of tamoxifen, emodin, and plumbagin was analyzed in BRCA1-silenced ovarian cancer cells that express ER (Srinivas et al. 2004a). It was observed that the induction of apoptosis was greater in BRCA1-blocked cells and the efficacy was in the order of plumbagin > tamoxifen > emodin.

In a myeloma model (Bringmann et al. 2008), it was first reported that plumbagin has no effect on proliferation of human multiple myeloma cells lines RPMI8226 and INA-6, as evaluated by Annexin V-FITC/PI staining. However, in a later study in myeloma cell lines U266 and MM.1S, it was shown that plumbagin can inhibit both constitutive and interleukin (IL-6)-inducible STAT-3 phosphorylation, leading to the induction of apoptosis (Sandur et al. 2010). These contrasting results suggest that plumbagin might have a cell-line specific effect in myeloma models.

In human melanoma 375.S2 cells, plumbagin has been reported to induce apoptosis and S-G2/M cell cycle arrest leading to cell growth inhibition (Wang et al. 2008). The anticancer effect of plumbagin was also verified in vivo. Plumbagin treatment resulted in elevated p21 levels and reduced levels of cyclin B1, cyclin A, Cdc2, and Cdc25C. It also induced a change in Bax/Bcl-2 ratios and activation of caspase-9 resulting in apoptotic cell death. In A-431 cells, it has been reported that the biological action of plumbagin is mediated through a mechanism that involves redox recycling of transition metal ion copper (Nazeem et al. 2009). There are some other reports on the anticancer ability of plumbagin against melanoma cells as well (Mandala Rayabandla et al. 2010; Prasad et al. 1996).

The effect of plumbagin on liver cancer HepG2 cells has been investigated and it was observed that plumbagin can inhibit the migration and invasion of liver cancer cells through down-regulation of MMP-2 and uPA (Shih et al. 2009). In another study (Parimala and Sachdanandam 1993), administration of plumbagin (4 mg/kg body weight) was found to significantly induce regression of tumor in 3-methyl-4-dimethyl aminoazobenzene (3MeDAB)-induced hepatoma in Wistar male rats. There is also a report on cytotoxic action of plumbagin against HEPA-3B hepatoma cells (Kuo et al. 1997). An anticancer action of plumbagin has been suggested against human embryonic kidney 293 (HEK293) cells (Ding et al. 2005) through inhibition of Nox-4, a renal NAD(P)H oxidase, activity.

Kuo et al. (1997) first demonstrated the anticancer effects of plumbagin against cervical carcinoma HeLa cells. In a later study, Srinivas et al. evaluated the anticancer effect of plumbagin against another human cervical cancer cell line, ME-180 (Srinivas et al. 2004b). These studies indicated that plumbagin is an effective inhibitor of cervical cancer cell growth. Plumbagin induced apoptosis through a caspase-dependent pathway. As a further confirmation, another study has also demonstrated a cytotoxic action of plumbagin against HeLa cells (Montoya et al.

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