Effect of Antioxidants Co-enzyme Q10 and β-carotene on the Cytotoxicity of Vemurafenib against Human Malignant Melanoma

Abstract

Melanoma is a type of highly invasive skin cancer derived from melanocyte with a poor prognosis. Clinical studies have shown that the most common mutation in malignant melanoma is BRAFV600E. Vemurafenib (PLX4032) is a clinically approved targeted drug for BRAF mutant melanoma that has a high therapeutic efficiency and significantly prolongs overall survival rate. However, most patients will become drug resistant and suffer from melanoma relapse within one year. Antioxidants have been widely used as supplements for cancer prevention and decreasing the side effects of cancer therapy. However, antioxidants could also protect cancer cells from oxidative stress and promote cell growth. This study aims to examine the effect of coenzyme Q10 and β-carotene on cell growth and invasion, and on the cytotoxicity of Vemurafenib against both Vemurafenib-sensitive and Vemurafenib-resistant human malignant melanoma cell lines. Results showed that coenzyme Q10 alone significantly reduced the viability and migration of human malignant melanoma cells. In addition, coenzyme Q10 alone inhibited the apoptosis induction in Vemurafenib-sensitive SK-MEL-28 cells. β-carotene alone did not affect the viability and apoptosis induction of melanoma cells; however, it inhibited cell mobility and invasiveness. Coenzyme Q10 enhanced the ability of Vemurafenib to decrease viability and mobility of melanoma cells. In contrast, β-carotene alleviated the cytotoxicity of Vemurafenib and mitigated the inhibitory effect of Vemurafenib on cell viability, mobility and invasion. Both coenzyme Q10 and β-carotene protected melanoma cells from undergoing apoptosis induced by Vemurafenib. β-carotene enhanced the suppression of Ras-Raf-Mek-Erk intracellular signaling pathway activation, which may contribute its inhibitory effect on cell mobility and invasiveness. Therefore, since it increases the cytotoxicity of Vemurafenib, coenzyme Q10 can potentially serve as an adjunct used together with anti-melanoma chemotherapy. However, due to alleviating anti-melanoma activities of Vemurafenib, β-carotene may not be appropriate supplements for melanoma patients who concurrently receive Vemurafenib as a targeted therapy.