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Biomedical subjects

W Bollag

Publications and source records attributed to W Bollag.

93 records · Page 6Linked to original sources

Retinoid receptors: pathways of proliferation inhibition and apoptosis induction in breast cancer cell lines.

In this study we investigated the effects of several selective agonist retinoids (specific for RAR alpha, RAR beta, RAR gamma, and RXR alpha, respectively) on the proliferation and apoptosis of human breast cancer cell lines. All these retinoids inhibit proliferation through apoptosis induction, but with some differences among the tested molecules and the three cell lines. In particular, estrogen receptor positive (ER+) cells display a higher sensitivity to RARs selective compounds, the RAR alpha selective compound being the most effective agent, while estrogen receptor negative (ER-) cells show a greater responsiveness to the RXR alpha selective retinoid. In all tested cell lines a potent antiproliferative and apoptotic effect was also displayed by a high dose of the RAR gamma selective compound. The apoptosis induction is associated with bcl-2 down-regulation, while p53 expression is not modified by any retinoid. Only in one cell line (ZR-75.1), after RAR alpha selective retinoid treatment is there an induction of RAR beta: therefore not only RAR beta induction but also other mechanisms may contribute to the growth inhibitory effect of retinoids in tested breast cancer cell lines.

Antineoplastic Agents↗

Vitamin A acid in benign and malignant epithelial tumours of the skin.

Vitamin A acid has a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumours in mice. Vitamin A acid, given orally, leads to a regression of established skin papillomas. Skin carcinomas too are influenced to a certain degree. Furthermore this substance, administered prophylactically, prevents or delays the appearance of skin papillomas and carcinomas. The mechanism of action is discussed.

9,10-Dimethyl-1,2-benzanthracene↗

Induction of apoptosis in MCF-7 breast carcinoma cell line by RAR and RXR selective retinoids.

Induction of apoptosis in MCF-7 breast carcinoma cell line by various retinoids was measured by cytofluorimetry and DNA fragmentation assay. Retinoids with marked or high selectivity for RAR alpha, RAR beta, RAR gamma or RXR alpha were tested. All these retinoids were capable of inducing apoptosis, in a dose- and time-dependent way. MCF-7 cell line expressed RAR alpha, RAR gamma and RXRs, but not RAR beta. Compared to untreated MCF-7 cells, after 2 days of incubation with each of the selective retinoids, a substantial increase in apoptotic cells was observed, even at the lowest concentration of 10(-8) M. Among the various analysed selective retinoids only slight differences were observed. All-trans retinoic acid and 13-cis retinoic acid induced apoptosis only after 6 days and 9-cis-retinoic acid after 4 days of incubation. Since all receptor selective retinoids substantially inducedapoptosis, it may be concluded that RAR alpha, RAR gamma and RXR alpha are able to mediate programmed cell death in the tested tumor cell line. Highly selective retinoid receptor agonists and antagonists may be useful for clarifying the function of retinoid receptors and for further progress in the field of cancer prevention and therapy by retinoids.

Apoptosis↗