Inhibition of Curcumin on ZAKα Activity Resultant in Apoptosis and Anchorage- Independent Growth in Cancer Cells

Abstract

Curcumin, a popular yellow pigment of the dietary spice turmeric, has been reported to inhibit cell growth and to induce apoptosis in a wide variety of cancer cells. Although numerous studies have investigated anticancer effects of curcumin, the precise molecular mechanism of action remains unidentified. Whereas curcumin mediates cell survival and apoptosis through mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling cascades, its impact on the upstream regulation of MAPK is unclear. The leucine-zipper and sterile-α motif kinase alpha (ZAKα), a mitogen-activated protein kinase kinase kinase (MAP3K), activates the c-Jun N-terminal kinase (JNK) and NF-κB pathway. This paper investigated the prospective involvement of ZAKα in curcumin-induced effects on cancer cells. Our results suggest that the antitumor activity of curcumin is mediated via a mechanism involving inhibition of ZAKα activity.

Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives

“…In ovarian cancers, there is an abnormal increase in the expression of sarco/endoplasmic reticulum calcium ATPase (SERCA) [ 92 ], which can regulate Ca 2+ homeostasis, and curcumin treatment has been found to suppress SERCA activity, leading to the disruption of Ca 2+ homeostasis, and apoptosis of ovarian cancer cells. Recent studies demonstrate that the activity of leucine-zipper and sterile-alpha motif kinase alpha (ZAKα) is inhibited by curcumin, suggesting the involvement of apoptosis induction by curcumin [ 93 ]. Also, in colorectal cancer cells, curcumin increases p53 expression in tumor cells and modulates the tumor cell apoptotic pathway, promoting apoptosis of tumor cells [ 94 ].…”

Curcumin attenuates endothelial cell fibrosis through inhibiting endothelial–interstitial transformation

“…43 Studies have shown that curcumin effectively inhibits the malignant behaviour of cancer cells and has broad applications in the treatment of cancer. 44,45 Curcumin also has many functions such as antibacterial, anti-inflammatory, analgesic and wound healing properties, and its immunomodulatory potential in many inflammatory disease models has been demonstrated. 46,47 Moreover, studies have shown that curcumin protects against myocardial fibrosis through various mechanisms.…”