Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.
针对黑色素瘤的系统性治疗方案中，临床指南推荐采用化疗药物靶向治疗及免疫检查点抑制剂疗法。尽管黑色素瘤治疗手段持续改进，但现有疗法仍面临耐药性问题。本研究旨在探讨藤黄酸对肿瘤增殖、凋亡等特异性生物学行为的影响。藤黄酸是从藤黄属植物山竹果中提取的天然化合物，是近期发现的潜在抗肿瘤药物。众多植物源性化合物已成为重要药物来源，例如从中国喜树树皮中提取的喜树碱衍生物，以及从短叶红豆杉树皮中提取的紫杉醇，均已应用于临床抗肿瘤治疗。本研究发现藤黄酸能显著抑制黑色素瘤细胞系增殖并诱导细胞凋亡。值得注意的是，表达细胞间黏附分子T-钙黏蛋白（CDH13）的阳性细胞对藤黄酸治疗表现出更高敏感性。通过siRNA池敲低T-钙黏蛋白表达后，细胞对藤黄酸的敏感性降低，其增殖能力和抗凋亡特性得以恢复。研究结论表明，T-钙黏蛋白阳性患者可能从藤黄酸治疗中获得显著临床获益。
The Role of T-Cadherin (CDH13) in Treatment Options with Garcinol in Melanoma
肿瘤(癌症)患者之家