Inhibition of growth and sensitization to cisplatin‐mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents

Abstract

The polyphenolic compounds curcumin and quercetin increased sensitivity of ovarian cancer cells (CAOV3 and SKOV3) to cisplatin. The effect was obtained when the compounds were added simultaneously with cisplatin, as well as when they were added 24 h before. High serum levels of certain cytokines, for example interleukin-6 (IL-6), have been associated with poor prognosis and cisplatin resistance in various forms of cancer. Furthermore, it has been hypothesized that cytokines may increase proliferation, metastasis, and stimulate production of detoxification enzymes and multi-drug resistant proteins. Curcumin inhibits the production of many cytokines. The two ovarian cell lines differ significantly in IL-6 production, and correspondingly the high producer, CAOV3, was less susceptible to cisplatin. Curcumin inhibited the production of IL-6 in this cell suggesting that one of the mechanisms for synergy between cisplatin and curcumin was by reducing the autologous production of IL-6. However, the synergy was also observed in the low IL-6 producer, SKOV3, indicating that the action was most probably a result of multiple targeting. In sum, this study suggests that the compounds, curcumin and quercetin, potentially may be useful for enhancing drug sensitivity in certain cancer.

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

“…Other studies have also reported a synergistic interaction between different treatment strategies (Liu et al, 2001;Kuhar et al, 2007;Kumi-Diaka et al, 2010;Wang et al, 2011). Other studies of concurrent curcumin and chemotherapeutic drugs such as cisplatin, doxorubicin, and taxol showed that curcumin enhances the antitumor activities of the latter in various cancer cells (Chan et al, 2003;Notarbartolo et al, 2005). SFN when used in combination with arsenic trioxide and doxorubicin augmented their growth inhibitory properties (Fimognari et al, 2007;Doudican et al, 2012).…”

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

“…Since NF-jB is also a transcription factor for inflammatory cytokines, curcumin has been demonstrated to attenuate the expression of IL-1, IL-6, and TNF-a [11]. Curcumin increased the sensitivity of SKOV3 and CAOV3 cells to cisplatin, and one of the suggested mechanisms was reducing the production of IL-6 [9]. In addition to inhibition of inflammatory cytokines, curcumin has also been shown to suppress angiogenic factors, such as VEGF, and subsequently inhibits angiogenesis in both in vitro and in vivo studies [36,63].…”

Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study

“…It exerts its effects via diverse biological properties, including, but not limited to, suppression of nuclear factor-kB and inhibition of angiogenesis (Arbiser et al, 1998;Aggarwal et al, 2003;Li et al, 2005). It also enhances the antitumor effects of several classic chemotherapeutic drugs, such as doxorubicin, cis-platinum, and paclitaxel (Chan et al, 2003;Bava et al, 2005). In spite of being a 'wonder molecule,' the therapeutic efficacy of curcumin is limited by poor aqueous solubility, chemical instability in alkaline medium, rapid metabolism, and poor absorption from the gastrointestinal tract (Anand et al, 2007).…”