bcl-2 inhibits mitochondrial metabolism and lonidamine-induced apoptosis in adriamycin-resistant mcf7 cells

✍ Scribed by Annamaria Biroccio; Donatella Del Bufalo; Maurizio Fanciulli; Tiziana Bruno; Gabriella Zupi; Aristide Floridi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 106 KB
• Volume: 82
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990702)82:1<125::aid-ijc21>3.0.co;2-q

✦ Synopsis

Lonidamine (LND), a selective inhibitor of the energy metabolism of tumor cells, induces apoptosis, independently of the p53 gene, in the adriamycin(ADR)-resistant MCF7 breast-cancer cell line (MCF7 ADR). On the contrary, LND fails to activate the apoptotic program in the parental MCF7-sensitive cell line (MCF7 WT). The extent of bcl-2 expression might account for the different effect of LND on these cell lines. In fact, the MCF7 ADR line shows a low level of bcl-2 protein, whereas MCF7 WT expresses a high level of bcl-2. We therefore investigated the relationship between the amount of bcl-2 and the ability of LND to induce apoptosis, using 4 clones over-expressing bcl-2. The effect of bcl-2 on the energy metabolism was also evaluated. We demonstrated that over-expression of bcl-2 inhibited LNDinduced apoptosis, while reducing 14 CO 2 production, oxygen uptake and ATP content, whereas aerobic lactate production was essentially unaffected. In addition, LND decreased the oxidative metabolism of the MCF7 ADR cells to a greater extent than it did in the bcl-2 transfectants. Int.