ANTI-MELANOMA ACTIVITY OF PERPHENAZINE AND PROCHLORPERAZINE IN HUMAN COLO829 AND C32 CELL LINES

Cutaneous melanoma is fairly common (only about 1% of skin cancers), but is the deadliest malignant tumor. Moreover, amelanotic type of melanoma is very difficult for clinical diagnosis. The standard therapy can cause a lot of side effects e.g. nausea, vomiting and headaches, which means that novel and effective strategies are required. Interestingly, phenothiazine derivatives possess sedative, antiemetic, and anticancer activity. In the present study, we explore the anticancer effect of perphenazine and prochlorperazine in human melanotic (COLO829) and amelanotic (C32) melanoma cells suggesting that prochlorperazine inhibits cell viability in a concentration-dependent manner, impairs migration, and decreases tyrosinase and MITF amount. Moreover, the analyzed drugs decrease/increase MITF amount depending on type of melanoma. We demonstrated that the decrease of MITF and tyrosinase protein induces migration inhibition of C32 cells, and suggests the ability of those drugs to restore cancer cell sensitivity to treatment. The ability of prochlorperazine to containing the spread of the amelanotic melanoma in vivo may be helpful in the development of a new and effective antimelanoma therapy.

皮肤黑色素瘤（cutaneous melanoma）虽仅占皮肤恶性肿瘤的1%左右，却是较为常见且致死性最强的恶性肿瘤。此外，无色素型黑色素瘤的临床诊断难度极高。常规治疗手段常引发诸多不良反应，如恶心、呕吐与头痛，因此亟需开发新型有效的治疗策略。值得注意的是，吩噻嗪类衍生物（phenothiazine derivatives）兼具镇静、止吐与抗癌活性。本研究探究了奋乃静（perphenazine）与丙氯拉嗪（prochlorperazine）对人有色素型（COLO829）及无色素型（C32）黑色素瘤细胞的抗癌活性，结果显示丙氯拉嗪可通过浓度依赖方式抑制细胞活力、损伤细胞迁移能力，并降低酪氨酸酶（tyrosinase）与小眼畸形相关转录因子（MITF）的表达量。此外，受试药物对MITF表达量的调控作用因黑色素瘤类型而异，可表现为上调或下调。本研究证实，MITF与酪氨酸酶蛋白水平的下调可抑制C32细胞的迁移能力，同时提示上述药物可恢复癌细胞对治疗的敏感性。丙氯拉嗪在体内可抑制无色素型黑色素瘤扩散的特性，有望为开发新型高效的抗黑色素瘤治疗方案提供新思路。