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

Abstract

Protein kinase C (PKC) has been considered for a potential target of anticancer chemotherapy. PKC-alpha has been associated with growth and metastasis of some cancer cells. However, the role of PKC-alpha in human breast cancer cell proliferation and anticancer chemotherapy remains unclear. In this study, we examined whether alterations of PKC-alpha 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-alpha, increased cancer cell proliferation and attenuated VIN (1 microM)-induced cytotoxicity. These effects were not affected in the presence of 10 nM staurosporine. Phorbol myristate acetate (PMA, 100 nM) that completely depleted PKC-alpha also enhanced cancer cell proliferation and attenuated VIN-induced cytotoxicity. Three potent PKC inhibitors, staurosporine (10 nM), chelerythrine (5 microM) 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 microM) 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-alpha.

• Authors: Daniel Sd Liu, Chad E Krebs, Shi J Liu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 101 Issue 2 Pg. 517-28 (May 15 2007) ISSN: 0730-2312 [Print] United States
• PMID: 17171646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carcinogens
• Enzyme Inhibitors
• Phorbol 12,13-Dibutyrate
• Vinblastine
• Doxorubicin
• Protein Kinase C-alpha
• Staurosporine

Topics

• Antineoplastic Agents (metabolism)
• Breast Neoplasms (metabolism)
• Carcinogens (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cell Shape
• Doxorubicin (metabolism)
• Enzyme Activation
• Enzyme Inhibitors (metabolism)
• Female
• Humans
• Phorbol 12,13-Dibutyrate (metabolism)
• Protein Kinase C-alpha (antagonists & inhibitors, metabolism)
• Staurosporine (metabolism)
• Vinblastine (metabolism)