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

Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study
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DOI:
10.3892/etm_00000089
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发表时间:
2010-07-01
影响因子:
2.7
通讯作者:
Kanekura, Takuro
Kanekura, Takuro
中科院分区:
医学4区
文献类型:
--
作者:
Matsushita, Shigeto;Tada, Ko-Ichi;Kanekura, Takuro

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恶性黑色素瘤(MM)是一种侵袭性化学耐药皮肤癌,其特征是快速转移和预后不良。因此,开发创新的有效疗法至关重要。MK 615是来自日本杏Prunus mime Sieb的提取物。Et Zucc(Ume).在中性pH值下,它含有天然化学物质,如三萜类化合物,在几种类型的癌症中发挥抗肿瘤作用。我们发现,在晚期MM患者中,MK 615显著抑制了疾病的皮肤转移。肿瘤治疗前后的比较显示,MK 615显著增加了凋亡指数。MTT法、流式细胞仪细胞周期分析和免疫荧光显微镜观察结果显示,MK 615可剂量依赖性地抑制SK-MEL 28细胞的生长,增加亚G1期细胞比例,诱导细胞凋亡。我们进一步检测了晚期糖基化终产物受体(AGEs)的表达。α-淀粉样蛋白是一种多配体受体,可与新型细胞因子高迁移率族蛋白1(HMGB 1)以及晚期糖基化终产物结合。有证据表明,MK 615/HMGB 1的相互作用增强MM细胞的侵袭。在这里,我们提出的Western印迹和免疫荧光显微镜数据表明,MK 615抑制SK-MEL 28细胞中的MK 615的表达,并抑制SK-MEL 28细胞释放HMGB 1。我们的研究结果表明,MK 615可能是治疗MM和其他恶性肿瘤的有价值的工具。
Malignant melanoma (MM) 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 mime 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 MM, 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 (RAGE). RAGE is a multi-ligand receptor that binds to a novel cytokine, high mobility group box protein 1 (HMGB1), as well as advanced glycation end products. There is evidence that RAGE/HMGB1 interactions enhance cell invasion in MM. Here, we present Western blotting and immunofluorescence microscopy data indicating that MK615 inhibited the expression of RAGE in SK-MEL28 cells, and suppressed the release of HMGB1 by SK-MEL28 cells. Our findings suggest that MK615 may be a valuable tool for treating MM and other malignant tumors.