Premium
Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG‐1 ovarian cancer cells
Author(s) -
Srinivas Gopal,
Annab Lois A.,
Gopinath Gokul,
Banerji Asoke,
Srinivas Priya
Publication year - 2004
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10164
Subject(s) - plumbagin , biology , apoptosis , antiestrogen , cancer cell , tamoxifen , emodin , ovarian cancer , in vitro , cancer research , pharmacology , cancer , breast cancer , biochemistry , genetics
Previous studies have shown that reduction in BRCA1 mRNA and protein can result in increased proliferation of BG‐1 ovarian cancer cells in both in vitro and in vivo conditions, suggesting that BRCA1 may normally act as a growth inhibitor in these cells. Also, there are other reports that suggest that wild‐type BRCA1 protein may repress estrogen receptor (ER) function either directly or indirectly. However, response to antiestrogen drugs in BRCA1‐blocked ER‐positive ovarian cancer cells has not been reported, and this served as the rationale for this study. We analyzed the effect of tamoxifen, emodin, and plumbagin in BRCA1‐blocked ER‐positive BG‐1 ovarian cancer cells. For all three drugs, BRCA1‐blocked cells were more sensitive than the corresponding control cells as assessed by MTT assay; however, only plumbagin showed a statistically significant difference in mean viability ( P < 0.05). All three drugs induced loss of mitochondrial membrane potential (ΔΨ m ), nuclear condensation, DNA fragmentation, and morphological changes, as observed after 6 h of drug treatment, suggesting apoptosis induction in both BRCA1‐blocked and control cells. However, apoptosis induction was greater in BRCA1‐blocked cells, the efficacy being in the order of plumbagin > tamoxifen > emodin. The dose of plumbagin needed to kill 50% was 5 μM in the control cells and 2.68 μM for the BRCA1‐blocked cells, indicating that the latter was about twofold more sensitive to plumbagin than the wild‐type cells. This throws light on the fact that plumbagin may have chemotherapeutic potential as an anticancer agent in BRCA1‐mutated ovarian cancer patients. © 2003 Wiley‐Liss, Inc.