Melanoma is an aggressive cancer with high lethality. In order to find new anticancer agents, isokotomolide A (Iso A) and secokotomolide A (Sec A) isolated from Cinnamomum kotoense were identified to be potential bioactive agents against human melanoma but without strong antioxidative properties. Cell proliferation assay displayed Iso A and Sec A treated in the normal human skin cells showed high viabilities. It also verified that two of them possess strong antimelanoma effect in concentration-dependent manners, especially on B16F10, A2058, MeWo, and A375 cells. Wound healing assay presented their excellent antimigratory effects. Through 3-N,3-N,6-N,6-N-Tetramethylacridine-3,6-diamine (acridine orange, AO) staining and Western blot, the autophagy induced by treatment was confirmed, including autophagy-related proteins (Atgs). By using annexin V–FITC/PI double-stain, the apoptosis was confirmed, and both components also triggered the cell cycle arrest and DNA damage. We demonstrated the correlations between the mitogen-activated protein kinase (MAPK) pathway and antimelanoma, such as caspase cascade activations. To further evaluate in vivo experiments, the inhibition of tumor cell growth was verified through the histopathological staining in a xenograft model. In this study, it was confirmed that Iso A and Sec A can encourage melanoma cell death via early autophagy and late apoptosis processes.

中文翻译：

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来自肉桂的异麦芽酮糖醇A诱导体内和体外黑色素瘤自噬和细胞凋亡。

黑色素瘤是一种具有高致死率的侵袭性癌症。为了找到新的抗癌药，从古肉桂中分离出的异麦芽酮糖醇A（Iso A）和仲麦芽糖酮A（Sec A）被认为是潜在的针对人黑素瘤的生物活性剂，但没有很强的抗氧化特性。细胞增殖试验显示，在正常人的皮肤细胞中处理的Iso A和Sec A具有很高的生存能力。还证实了它们中的两个以浓度依赖的方式具有强烈的炭疽瘤作用，尤其是对B16F10，A2058，MeWo和A375细胞。伤口愈合试验显示了其出色的抗迁移效果。通过3- N，3- N，6- N，6- N-四甲基ac啶-3,6-二胺（ac啶橙，AO）染色和蛋白质印迹，证实了由处理诱导的自噬，包括自噬相关蛋白（Atgs）。通过使用膜联蛋白V–FITC / PI双重染色，证实了细胞凋亡，并且这两个成分也触发了细胞周期停滞和DNA损伤。我们证明了有丝分裂原激活的蛋白激酶（MAPK）途径和anlanlanoma，如胱天蛋白酶级联激活之间的相关性。为了进一步评估体内实验，通过在异种移植模型中的组织病理学染色证实了对肿瘤细胞生长的抑制。在这项研究中，已证实Iso A和Sec A可以通过早期自噬和晚期凋亡过程促进黑色素瘤细胞死亡。