Effect of antioxidants coenzyme 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 melanocytes with poor prognosis. Vemurafenib (PLX4032) is a clinically approved targeted therapeutic for BRAF mutant melanoma that has a high therapeutic response rate and significantly prolongs the overall survival time of patients with melanoma. Antioxidants have been widely used as supplements for cancer prevention and for decreasing the side effects of cancer therapy. However, antioxidants can also protect cancer cells from oxidative stress and promote cancer growth and progression. The present study aimed to examine the effect of the antioxidants coenzyme Q10 (CoQ10) and β-carotene on melanoma cell growth and invasiveness and on the cytotoxicity of vemurafenib against both vemurafenib-sensitive (SK-MEL-28) and vemurafenibresistant (A2058) human malignant melanoma cell lines. MTS assay and wound-healing assay demonstrated that CoQ10 alone significantly reduced the viability and migration of melanoma cells, respectively, and synergistically worked with vemurafenib to decrease the viability and migration of human melanoma cells. In contrast, MTS assay and flow cytometry revealed that β-carotene alone did not affect the viability and apoptosis induction of melanoma cells; however, it inhibited cell migration and invasiveness. Wound-healing and Transwell assay demonstrated that β-carotene alleviated the cytotoxicity of vemurafenib and mitigated the inhibitory effect of vemurafenib on cell migration and invasion. Both CoQ10 and β-carotene protected melanoma cells from undergoing apoptosis induced by vemurafenib. Immunoblotting demonstrated that β-carotene at physiological concentration worked synergistically with vemurafenib to suppress the Ras-Raf-Mek-Erk intracellular signaling pathway. The present study aimed to add to the evidence of the in vitro effects of CoQ10 and β-carotene on the antimelanoma effects of vemurafenib.

Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells

“…This implies that STIG may be a promising agent to treat melanoma (Figure 8). Previous studies have suggested the use of antioxidants for melanoma prevention or treatment [43,50]. The skin is continuously exposed to exogenous oxidative stress, with melanocytes particularly vulnerable due to the melanogenesis process, which generates ROS [51].…”

“…Lowering local ROS levels enhances the immune response to melanoma by inhibiting PD-L1 signaling in vivo [53,57]. Quercetin is excellent Previous studies have suggested the use of antioxidants for melanoma prevention or treatment [43,50]. The skin is continuously exposed to exogenous oxidative stress, with melanocytes particularly vulnerable due to the melanogenesis process, which generates ROS [51].…”

Energy Metabolism as a Therapeutic Target in Cancer: The Role of Coenzyme Q10

“…For example, the administration of CoQ10 in a breast cancer cell line reduced the activity of matrix metalloproteinase II, a key promotor of cancer cell invasion and metastasis [85]. In cultured melanoma cells, CoQ10 demonstrated an inhibitory effect on cell proliferation and migration/invasion when used individually or in combination with vemurafenib, despite an apparent protective effect of CoQ10 in protecting melanoma cells from apoptosis induction [86]. In a rat temozolomide-resistant glioma cell line, the co-administration of CoQ10 increased the efficacy of temozolomide in reducing cell proliferation and invasiveness [87].…”

Chemical Composition, Functional and Anticancer Properties of Carrot

“…On the contrary, β-carotene did not exhibit anti-proliferative effects on melanoma cells. It was demonstrated that β-carotene alone (1 µM) did not affect BRAF or ERK expression in melanoma cell lines carrying the B-RAF mutation (A2058 cell line), while in combination with B-RAFi (PLX), it enhanced the suppression of B-RAF activation and of the downstream Erk1/2 effector, induced by PLX [92], suggesting its potential use as an adjuvant for target-based therapy.…”

“…Anti-proliferative, anti-inflammatory, anti-apoptotic, anti-metastatic, ABC efflux transporter modulator [89][90][91][92]97] Antocianins Cytotoxic [93] 6-Methoximellein Anti-inflammatory, anti-metastatic [94] Falcarinol (FaOH)…”