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.
Toma
S
S
National Institute for Cancer Research (IST), Department of Medical Oncology, University of Genoa, Italy.
Isnardi
L
L
Riccardi
L
L
Bollag
W
W
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000187:drug effects* / Q000502:physiology; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors