Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents

Thasni Karedath Abdul Azis, S. Rakesh, G. Rojini, T. Ratheeshkumar, G. Srinivas, S. Priya

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: Cellular response to chemotherapeutic drugs in the absence of BRCA1 either completely or partially had drawn less attention. The present study evaluated whether there is a differential inhibition of cell growth by selected compounds with respect to BRCA1 status in estrogen receptor (ER)-positive ovarian cancer cells. Materials and methods: The BG1 ovarian cancer cells used in the experiments were antisensely blocked with BRCA1 gene. Growth inhibition and apoptotic induction were analyzed to evaluate the cytotoxic effects. Small interfering RNA (SiRNA) transfection, western blot analysis, RT-PCR analysis and molecular modeling were carried out to analyze the estrogen-dependent action of plumbagin. Results: Although we found that all the compounds studied induce apoptosis, the induction was in the order of plumbagin > doxorubicin > tamoxifen > cisplatin. Plumbagin can bind to the active site of ER-α. Plumbagin, however, induced ER-α 46 kDa truncated isoform, which was found abundantly preempted in the cytoplasm compared with a 66-kDa full-length isoform. The truncated isoform is known to inhibit classical ER-α signaling pathways. SiRNA-transfected cells for ER-α exhibited lower cytotoxicity upon plumbagin treatment than the control-transfected cells. Conclusion: Taken together, this study indicates that plumbagin has chemotherapeutic potential in BRCA1-mutated/defective ER-positive cancers.

Original languageEnglish
Pages (from-to)696-705
Number of pages10
JournalAnnals of Oncology
Volume19
Issue number4
DOIs
Publication statusPublished - 1 Apr 2008
Externally publishedYes

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Estrogen Receptors
Ovarian Neoplasms
Estrogens
Apoptosis
Protein Isoforms
Small Interfering RNA
BRCA1 Gene
Tamoxifen
Growth
Doxorubicin
Cisplatin
Transfection
plumbagin
Catalytic Domain
Cytoplasm
Western Blotting
Polymerase Chain Reaction
Pharmaceutical Preparations
Neoplasms

Keywords

  • BRCA1
  • Cisplatin
  • Doxorubicin
  • Plumbagin
  • Tamoxifen

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents. / Karedath Abdul Azis, Thasni; Rakesh, S.; Rojini, G.; Ratheeshkumar, T.; Srinivas, G.; Priya, S.

In: Annals of Oncology, Vol. 19, No. 4, 01.04.2008, p. 696-705.

Research output: Contribution to journalArticle

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