Differential Regulation of Apoptosis in Normal versus Transformed Mammary Epithelium by Lutein and Retinoic Acid

Differential Regulation of Apoptosis in Normal versus Transformed Mammary Epithelium by Lutein and Retinoic Acid1

Department of Internal Medicine and Comprehensive Cancer Center, Cancer and Geriatrics Center, University of Michigan, Ann Arbor, Michigan 48109-0942

Abstract

We examined the effects of all-trans retinoic acid (ATRA) and lutein (a nonprovitamin A carotenoid), on apoptosis and chemosensitivity in primary normal human mammary epithelial cells, SV40 transformed mammary cells, and MCF-7 human mammary carcinoma cells. ATRA and lutein selectively induced apoptosis in transformed but not normal human mammary cells. In addition, both compounds protected normal cells, but not transformed cells, from apoptosis induced by the chemotherapy agents etoposide and cisplatin. Furthermore, lutein and ATRA selectively increased the ratio of Bcl-xL:Bax protein expression in normal cells but not transformed mammary cells, suggesting a possible mechanism for selective modulation of apoptosis. The differential effects of lutein and ATRA on apoptotic pathways in normal versus transformed mammary epithelial cells may have important implications for chemoprevention and therapy.

Footnotes

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↵1 This work was supported by NIH Grants CA 61777-01 and CA 66233.
↵2 To whom requests for reprints should be addressed, at Department of Internal Medicine and Comprehensive Cancer Center, Room 6302, Cancer and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109-0942. Phone: (734) 936-1831; Fax: (734) 615-3947; E-mail: mwicha{at}umich.edu
↵3 The abbreviations used are: ATRA, all-trans retinoic acid; THF, tetrahydrofuran; MSU-1, Michigan State University-1 medium; SRF, serum replacement factor; PI, propidium iodide; CDDP, cisplatin.
- Accepted December 17, 1999.
- Received June 21, 1999.
- Revision received November 10, 1999.