Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.
Int J Mol Sci. 2021 Nov 4;22(21):11966. doi: 10.3390/ijms222111966.
Malignant melanoma is responsible for the majority of skin cancer-related deaths. The methods of cancer treatment include surgical removal, chemotherapy, immunotherapy, and targeted therapy. However, neither of these methods gives satisfactory results. Therefore, the development of new anticancer therapeutic strategies is very important and may extend the life span of people suffering from melanoma. The aim of this study was to examine the effect of ketoprofen (KTP) and UVA radiation (UVAR) therapy on cell proliferation, apoptosis, and cell cycle distribution in both melanotic melanoma cells (COLO829) and human melanocytes (HEMn-DP) in relation to its supportive effect in the treatment of melanoma. The therapy combining the use of pre-incubation with KTP and UVAR causes a significant increase in the anti-proliferative properties of ketoprofen towards melanoma cells and the co-exposure of melanotic melanoma cells induced apoptosis shown as the mitochondrial membrane breakdown, cell-cycle deregulation, and DNA fragmentation. Moreover, co-treatment led to GSH depletion showing its pro-apoptotic effect dependent on ROS overproduction. The treatment did not show a significant effect on normal cells-melanocytes-which indicates its high selectivity. The results suggest a possible benefit from the use of the ketoprofen and ultraviolet A irradiation as a new concept of melanotic melanoma therapy.
恶性黑色素瘤是导致大多数皮肤癌相关死亡的原因。癌症治疗方法包括手术切除、化疗、免疫疗法和靶向治疗。然而,这些方法都没有令人满意的效果。因此,开发新的抗癌治疗策略非常重要,可能会延长患有黑色素瘤的人的寿命。本研究旨在探讨酮洛芬(KTP)和长波紫外线辐射(UVAR)联合治疗对黑素瘤细胞(COLO829)和人黑素细胞(HEMn-DP)细胞增殖、凋亡和细胞周期分布的影响,并探讨其在治疗黑色素瘤中的辅助作用。联合使用预孵育 KTP 和 UVAR 的治疗方法可显著提高酮洛芬对黑素瘤细胞的抗增殖特性,并诱导黑素瘤细胞发生凋亡,表现为线粒体膜破裂、细胞周期失调和 DNA 片段化。此外,共同处理导致 GSH 耗竭,表明其依赖于 ROS 过度产生的促凋亡作用。该治疗方法对正常细胞-黑素细胞-没有显示出显著的作用,这表明其具有很高的选择性。研究结果表明,酮洛芬和紫外线 A 照射的联合使用可能是一种治疗恶性黑色素瘤的新方法。