Novel augmentation by bufalin of protein kinase C-induced cyclooxygenase-2 and IL-8 production in human breast cancer cells.
Cyclooxygenase-2 (COX-2) and IL-8 are two inflammatory mediators induced by protein kinase C (PKC) via various stimuli. Both contribute significantly to cancer progression. Bufalin, a major active component of the traditional Chinese medicine Chan Su, is known to induce apoptosis in various cancer cells. This study clarifies the role and mechanism of bufalin action during PKC regulation of COX-2/IL-8 expression and investigates the associated impact on breast cancer. Using MB-231 breast cancer cells, bufalin augments PKC induction of COX-2/IL-8 at both the protein and mRNA levels, and the production of prostaglandin E2(PGE2) and IL-8. The MAPK and NF-κB pathways are involved in both the PKC-mediated and bufalin-promoted PKC regulation of COX-2/IL-8 production. Bufalin increases PKC-induced MAPKs phosphorylation and NF-κB nuclear translocation. PGE2stimulates the proliferation/migration of breast cancer cells. Furthermore, PKC-induced matrix metalloproteinase 3 expression is enhanced by bufalin. Bufalin significantly enhances breast cancer xenograft growth, which is accompanied by an elevation in COX-2/IL-8 expression. In conclusion, bufalin seems to promote the inflammatory response in vitro and in vivo, and this occurs, at least in part, by targeting the MAPK and NF-κB pathways, which then enhances the growth of breast cancer cells.
1 Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsiao-Ting
HT
Chen
2 Department of Obstetrics and Gynecology, Cheng Hsin General Hospital, Taipei, Taiwan.
David
D
Sun
3 Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Yen-Chun
YC
Peng
1 Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Pu-Hong
PH
Kao
1 Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Yuh-Lin
YL
Wu
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002018:Bufanolides / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000473:pathology; D008516:Medicine, Chinese Traditional; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D002018:Bufanolides; D052246:Cyclooxygenase 2 Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone; C022777:bufalin
Inflammation; breast cancer; bufalin; cyclooxygenase-2; interleukin-8; signal transduction