The Role of T-Cadherin (CDH13) in Treatment Options with Garcinol in Melanoma

Simple Summary Malignant melanoma is the deadliest form of skin cancer. Since resistance and relapse to established therapy regimes for the treatment of malignant melanoma still occur frequently, the development of novel therapeutics is the key to improve patient prognosis. The study aimed to understand the function of the natural compound Garcinol on melanoma cells to contribute to its potential use in tumor therapy. We could show that Garcinol reduced proliferation and induced apoptosis in melanoma cells. Furthermore, we showed that melanoma cells expressing T-cadherin (CDH13) respond more sensitively to garcinol treatment. We postulate, that particularly T-cadherin-positive-patients could be receptive to garcinol therapy.Abstract 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.