In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids.
Both estrogen-receptor (ER) positive MCF-7 and ER-negative Hs578T and MDA-MB-231 human breast cancer cells were treated with carotenoids (beta-carotene, canthaxanthin and lycopene) and retinoids (all-trans-, 9-cis- and 13-cis-retinoic acid and all-trans-retinol). Among carotenoids, beta-carotene significantly reduced the growth of MCF-7 and Hs578T cells, and lycopene inhibited the growth of MCF-7 and MDA-MB-231 cells. Canthaxanthin did not affect the proliferation of any of the three cell lines. All-trans- and 9-cis-retinoic acid significantly reduced the growth of both MCF-7 and Hs578T cells, whereas 13-cis-retinoic acid and all-trans-retinol had a significant effect only on MCF-7 cells. MCF-7 and Hs578T cells treated with all-trans-retinoic acid (all-t-RA) were further studied for the mechanism behind growth inhibition. Retinoic acid receptors alpha and gamma (RARalpha, gamma) in MCF-7 cells and RARalpha, beta and gamma in Hs578T cells were not induced by all-t-RA treatment at either the protein or mRNA level. Hs578T cells treated with all-t-RA had significantly more cells in the G0/G1 stage of the cell cycle, but the same was not observed for MCF-7 cells. All-t-RA induced a dose-dependent cell death in MCF-7 cells, which may be a necrotic phenomenon. These results demonstrate that ER status is an important, although not essential factor for breast cancer cell response to carotenoid and retinoid treatments, and the mode of action of all-t-RA in MCF-7 and Hs578T cells is not through the induction of RAR. Other mechanistic pathways that are either followed by or concomitant with growth inhibition are possible.
Prakash
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Department of Biochemistry, School of Medicine, Tufts University, Boston, MA 02111-1837, USA. pankaj@silicoinsights.com
Russell
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RM
Krinsky
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D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000188:drug therapy*; D016644:Canthaxanthin / Q000627:therapeutic use; D002338:Carotenoids / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects*; D012176:Retinoids / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000975:Antioxidants; D011960:Receptors, Estrogen; D012176:Retinoids; D002338:Carotenoids; D016644:Canthaxanthin