Proliferation of human breast cancer cells and anti-cancer action of doxorubicin and vinblastine are independent of PKC-α

✍ Scribed by Daniel SD Liu; Chad E. Krebs; Shi J. Liu

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 608 KB
• Volume: 101
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21202

✦ Synopsis

Abstract

Protein kinase C (PKC) has been considered for a potential target of anticancer chemotherapy. PKC‐α has been associated with growth and metastasis of some cancer cells. However, the role of PKC‐α in human breast cancer cell proliferation and anticancer chemotherapy remains unclear. In this study, we examined whether alterations of PKC‐α by phorbol esters and PKC inhibitors could affect proliferation of human breast cancer MCF‐7 cells and the cytotoxic effect of chemotherapeutic agents. Exposure for 24 h to doxorubicin (DOX) and vinblastine (VIN) caused a concentration‐dependent reduction in proliferation of MCF‐7 cells. However, these two anticancer drugs altered cellular morphology and growth pattern in distinct manners. Phorbol 12,13‐dibutyrate (PDBu, 100 nM), which enhanced activities of PKC‐α, increased cancer cell proliferation and attenuated VIN (1 µM)‐induced cytotoxicity. These effects were not affected in the presence of 10 nM staurosporine. Phorbol myristate acetate (PMA, 100 nM) that completely depleted PKC‐α also enhanced cancer cell proliferation and attenuated VIN‐induced cytotoxicity. Three potent PKC inhibitors, staurosporine (10 nM), chelerythrine (5 µM) and bisindolylmaleimide‐I (100 nM), had no significant effect on MCF‐7 cell proliferation; staurosporine and chelerythrine, but not bisindolylmaleimide‐I, attenuated VIN‐induced cytotoxicity. Moreover, neither phorbol esters nor PKC inhibitors had an effect on cytotoxic effects of DOX (1 µM) on MCF‐7 cell proliferation. Thus, these data suggest that MCF‐7 cell proliferation or the anti‐cancer action of DOX and VIN on breast cancer cells is independent of PKC‐α. J. Cell. Biochem. 101: 517–528, 2007. © 2006 Wiley‐Liss, Inc.