Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB in breast cancer cells and potentiates the growth inhibitory effect of paclitaxel in a breast cancer nude mice model.
Most anticancer agents activate nuclear factor kappa B (NF-kappaB), which can mediate cell survival, proliferation, and metastasis. Curcumin has been shown to inhibit the growth of various cancer cells, without toxicity to normal cells. The antitumor effects of curcumin could be due in part to the inactivation of NF-kappaB. We hypothesize that blocking NF-kappaB activity may augment paclitaxel cancer chemotherapy. In this study, we investigated whether the inactivation of NF-kappaB by curcumin would enhance the efficacy of paclitaxel for inhibiting breast cancer growth in vitro and in vivo. We confirmed that curcumin inhibited paclitaxel-induced activation of NF-kappaB and potentiated the growth inhibitory effect of paclitaxel in MDA-MB-231 breast cancer cells. The combination of curcumin with paclitaxel elicited significantly greater inhibition of cell growth and more apoptosis, compared with either agent alone. In an experimental breast cancer murine model using MDA-MB-231 cells, combination therapy with paclitaxel and curcumin significantly reduced tumor size and decreased tumor cell proliferation, increased apoptosis, and decreased the expression of matrix metalloprotease 9 compared with either agent alone. These results clearly suggest that a curcumin-paclitaxel combination could be a novel strategy for the treatment of breast cancer.
Kang
Hee Joon
HJ
Division of Breast & Endocrine Surgery, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Dongan-Gu, Anyang, Korea.
Lee
Sang Hun
SH
Price
Janet E
JE
Kim
Lee Su
LS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D017239:Paclitaxel / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D016328:NF-kappa B; D003474:Curcumin; D017239:Paclitaxel