Curcumin Suppresses the Paclitaxel-Induced Nuclear Factor-κB in Breast Cancer Cells and Potentiates the Growth Inhibitory Effect of Paclitaxel in a Breast Cancer Nude Mice Model

Abstract

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.

Experimental Therapeutics for the Treatment of Triple Negative Breast Cancer

“…Mechanistic studies showed that the combination decreased the expression of MMP-9 and increased apoptosis in the tumors of treated mice. Interestingly, the dose of paclitaxel was much lower (7 mg/kg) than previously reported as a single treatment (Kang et al, 2009). Success has also been shown using in vitro combination studies.…”

Curcuma zedoaria (Berg.) Rosc. essential oil and paclitaxel synergistically enhance the apoptosis of SKOV3 cells

“…Yang et al (25) previously demonstrated that luteolin could enhance PTX-induced apoptosis in MDA-MB-231 human breast cancer cells, by blocking signal transducer and activator of transcription 3. Hossein et al (19) showed that PectaSol-C modified citrus pectin could sensitize ovarian cancer cells to PTX by inducing apoptosis, which may lead to an accumulation of cells in the subG 1 and G 1 phases, and cleavage of caspase-3 (24)(25)(26)(27). Numerous studies have reported that CZEO is a promising antitumor drug, which has a direct cytotoxic effect that inhibits tumor cell growth and proliferation, disrupts nuclear metabolism, inhibits angiogenesis and impairs the membrane potential, all of which can be lethal to cancer cells (3,15,28).…”

Paclitaxel-induced apoptosis is blocked by camptothecin in human breast and pancreatic cancer cells

“…the cellular processes controlling synergy or antagonism between cancer therapeutic agents used in combination are currently the subject of intense investigation (2,(22)(23)(24)(25). As many cancers do not fully respond to single-agent treatment, the development of a combination therapy utilizing two common and potent chemotherapeutics such as ptX and a topo I inhibitor holds enormous potential for the treatment of several malignancies.…”