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Year : 2004  |  Volume : 36  |  Issue : 4  |  Page : 238-243

Morphological and biochemical basis of centchroman as a novel antineoplastic agent in MCF-7 human breast cancer cells

Tissue Culture Laboratory, National Laboratory Animal Centre, Central Drug Research Institute, Lucknow - 226 001, India

Correspondence Address:
Anil K Balapure
Tissue Culture Laboratory, National Laboratory Animal Centre, Central Drug Research Institute, Lucknow - 226 001
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Source of Support: None, Conflict of Interest: None

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OBJECTIVE: To investigate the antineoplastic potential of a novel antiestrogen (AE) centchroman (CENT) using cell morphology, viability and cathepsin-D (Cath-D) gene expression as indices in MCF-7 human breast cancer cell line. MATERIAL AND METHODS: MCF-7 cells were incubated with CENT (1 ÁM, 10 ÁM) in the absence and presence of 17- estradiol (E2, 10 nM) for 4 days. Investigations were carried out on alterations in cell morphology, number, Cath-D gene expression using Phase Contrast Microscopy, Trypan-blue dye exclusion and spectrophotometric assay. A standard antiestrogen and antibreast cancer agent tamoxifen (TAM -1 ÁM, 10 ÁM) was used as a positive control. RESULTS: E2 (10 nM) alone significantly up-regulated the cells morphologically, numerically and biochemically thus establishing their hormonal responsiveness. TAM and CENT at 1 ÁM each enhanced and reduced the viable cell number respectively whereas both elevated the Cath-D activity. However, 35mm photographic evidence did not indicate any cytotoxic effect with either drug as compared to control. Addition of E2 to the two ligands separately affected the three parameters similar to that in E2 alone. With 10 ÁM TAM and CENT individually, the cells were visually devastated and so were the viable cell numbers and Cath-D gene expression. Supplementation of E2 under similar conditions failed to undo the damage to the cells morphologically and quantitatively. However, disparate results were observed with regards to the enzyme activity where TAM+E2 caused inhibition and CENT+E2 resulted in an induction. CONCLUSION: It can be concluded that both the AEs TAM and CENT displayed similarities in their antineoplastic action on MCF-7 cells as observed by morphological and viability studies except that the latter proved cytotoxic even at 1ÁM concentration. TAM and CENT showed a similar effect on Cath-D gene expression except at the higher dose (10 ÁM). These results suggest that the antiestrogen CENT has better antineoplastic potential as opposed to TAM.


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