Advanced malignant melanoma responds to Prunus mume sieb. Et Zucc (Ume) extract: Case report and in vitro study

Abstract

Malignant melanoma (MMMM) is an aggressive chemoresistant skin cancer characterized by rapid metastasis and a poor prognosis. Therefore, the development of innovative effective therapies is critical. MK615 is an extract from the Japanese apricot Prunus mume Sieb. Et Zucc (Ume). At a neutral pH, it contains natural chemical substances such as triterpenoids that exert anti-neoplastic effects in several types of cancers. We found that in patients with advanced MMMM, MK615 dramatically suppressed the cutaneous in-transit metastasis of the disease. Pre- and post-treatment comparison of tumors showed that the apoptotic index was significantly increased by MK615. In vitro studies, MTT assay, flow cytometric cell cycle analysis and immunofluorescence microscopy revealed that MK615 inhibited the growth of SK-MEL28 cells in a dose-dependent manner, increased the proportion of cells in sub-G1 phase and induced apoptosis. We further examined the expression of the receptor for advanced glycation end products (RARAGE). RARAGE is a multi-ligand receptor that binds to a novel cytokine, high mobility group box protein 1 (HMHMGB1), as well as advanced glycation end products. There is evidence that RARAGE/HMHMGB1 interactions enhance cell invasion in MMMM. Here, we present Western blotting and immunofluorescence microscopy data indicating that MK615 inhibited the expression of RARAGE in SK-MEL28 cells, and suppressed the release of HMHMGB1 by SK-MEL28 cells. Our findings suggest that MK615 may be a valuable tool for treating MMMM and other malignant tumors.