Evaluating the Anti-cancer Efficacy of a Synthetic Curcumin Analog on Human Melanoma Cells and Its Interaction with Standard Chemotherapeutics

Abstract

Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen.

Natural Health Products (NHP’s) and Natural Compounds as Therapeutic Agents for the Treatment of Cancer; Mechanisms of Anti-Cancer Activity of Natural Compounds and Overall Trends

“…Curcumin ( Figure 2 D) is a major constituent of turmeric and has been shown to possess anti-cancer effects against multiple cancer cell lines [ 39 ]. Pignanelli et al have shown that by inducing oxidative stress, two analogs of curcumin were capable of selectively inducing apoptosis in MDA-MB-231, MDA-MB-468, and SUM149, three triple-negative breast cancer cell lines, in-vitro.…”

“…NHPs such as dandelion root extract [ 52 ] have shown anti-cancer cytotoxicity. Purified compounds such as curcumin [ 53 ] and curcumin analogs [ 39 ], and vincristine and vinblastine [ 54 ] have also shown anti-cancer effects. In order to search for effective complementary treatments for this aggressive cancer, many NHPs and purified compounds are currently being tested in combination with chemotherapeutic drugs in both the pre-clinical and clinical phase.…”

“…Found within turmeric, curcumin is a purified compound derived from the Curcuma longa plant which has demonstrated anti-cancer effects [ 39 ]. Curcumin has been shown to selectively target melanoma cancer cells by altering the activity of signalling molecules and inducing inflammation pathways.…”

“…Curcumin has been shown to selectively target melanoma cancer cells by altering the activity of signalling molecules and inducing inflammation pathways. Unfortunately, when tested using in-vivo mouse models, it showed poor bioavailability [ 39 ]. Chemical analogues of curcumin such as Compound A were developed as they were more stable and efficacious while showing anti-cancer effects against human melanoma cells either alone or combined with contemporary chemotherapeutics such as paclitaxel [ 39 ].…”

“…Preclinical combinatory work of NHP and standard chemotherapeutics on melanoma has demonstrated positive results. Compound A, a curcumin analog, has shown it may have a small additive effect and no negative interaction with chemotherapeutics paclitaxel and cisplatin in-vitro [ 39 ]. In another study, a similar curcumin analog DM-1 observed promising in-vivo tumour reductions via intrinsic apoptosis in both monotherapy and in combination with dacarbazine [ 93 ].…”