Natural product corynoline is a unique isoquinoline alkaloid extracted from traditional Chinese medicine Corydalis bungeana Turcz, whereas its anticancer properties have not been investigated. In this study, we found that corynoline potently impairs the growth of melanoma cells, B16F10, and A375 in a concentration‐dependent manner. Treatment of melanoma cells with corynoline results in G2 cell arrest accompanied by reduced cdc2 activation. Furthermore, corynoline triggers apoptosis of melanoma cells, which is associated with increased expression of Bax and cleaved caspase‐3. Mechanistic study indicates that corynoline strongly induces reactive oxygen species (ROS) generation and subsequent DNA damage as evidenced by γ‐H2AX accumulation. Notably, the effect of corynoline on melanoma cell cycle and apoptosis is abolished by a ROS scavenger N‐acetyl cysteine (NAC), indicating a ROS‐dependent mechanism. Finally, corynoline significantly inhibits in vivo B16F10 melanoma tumor growth accompanied by reduced expression of Ki‐67 in tumor tissue. Taken together, our data suggest that corynoline suppresses melanoma cell growth in vitro and in vivo by inducing oxidative stress and represents a potential therapeutic agent for melanoma patients.

中文翻译：

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天然产物corynoline通过诱导氧化应激抑制黑色素瘤细胞生长

天然产物corynoline 是一种独特的异喹啉生物碱，从中药延胡索中提取，但其抗癌特性尚未得到研究。在这项研究中，我们发现 corynoline 以浓度依赖性方式有效地损害黑色素瘤细胞、B16F10 和 A375 的生长。用 corynoline 处理黑色素瘤细胞会导致 G2 细胞停滞并伴随着 cdc2 活化降低。此外，corynoline 触发黑色素瘤细胞的凋亡，这与 Bax 和裂解的 caspase-3 表达增加有关。机理研究表明，如γ-H2AX 积累所证明的那样，corynoline 强烈诱导活性氧 (ROS) 生成和随后的 DNA 损伤。尤其，corynoline 对黑色素瘤细胞周期和细胞凋亡的影响被 ROS 清除剂 N-乙酰半胱氨酸 (NAC) 消除，表明存在 ROS 依赖性机制。最后，corynoline 显着抑制体内 B16F10 黑色素瘤肿瘤生长，同时降低肿瘤组织中 Ki-67 的表达。总之，我们的数据表明，corynoline 通过诱导氧化应激在体外和体内抑制黑色素瘤细胞生长，并代表了黑色素瘤患者的潜在治疗剂。