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

Krishan Parashar,Christopher Pignanelli,Colin Curran,Guang Liang,Yi Wang,Christopher Nguyen,Siddhartha Sood,Jianzhang Wu,Siyaram Pandey,Caleb Vegh,Ali Mehaidli

doi:10.3390/molecules24132483

Krishan Parashar, Christopher Pignanelli + Show 9 more

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https://doi.org/10.3390/molecules24132483

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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.

Highlights

Melanoma is an aggressive malignancy that emerges from the uncontrolled division of melanocytes and contributes to the larger part of skin cancer deaths [1]
The objective of this study was to investigate the efficacy of novel synthetic curcumin analogs against human melanoma cells and demonstrate the possible mechanism of induction of apoptosis
We investigated if G361 cells undergoing apoptosis induced by and curcumin h stained withmitochondrial tetramethylrhodamine methyl ester indicator of

Summary

Introduction

Melanoma is an aggressive malignancy that emerges from the uncontrolled division of melanocytes and contributes to the larger part of skin cancer deaths [1]. Melanoma is treatable by surgical removal if detected early [5]. Tend to metastasize to lymph nodes and spread to other parts of the body [5,6]. Further treatment options include chemotherapy, radiation, and immunotherapy [7]. Most chemotherapies are genotoxic or target cytoskeleton structures in cancer cells to induce cell death. This targeting is nonselective as it kills normal cells, which leads to severe toxicity

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