World Health Organization data indicate a continuous increase in melanoma incidence, with metastatic melanoma characterized by poor prognosis and drug resistance. The exploration of therapeutics derived from natural products remains an active area of in vitro research. The aim of this study was to determine the antitumor effects of picrasidine I, a natural compound extracted from Picrasma quassioides, against two melanoma cell lines. We selected two metastatic melanoma cell lines, HMY‐1 and A2058, for molecular studies, including Western blotting, 4′,6‐diamidino‐2‐phenylindole staining, and flow cytometry. Picrasidine I demonstrated cytotoxic effects against the HMY‐1 and A2058 melanoma cell lines. It induced cell cycle arrest in the sub‐G1 phase and downregulated cell cycle–related proteins (e.g., cyclin A2, D1, cyclin‐dependent kinases 4, and 6). In the intrinsic apoptosis pathway, picrasidine I activated proapoptotic proteins (e.g., Bax, Bak, t‐Bid, BimL/S) and suppressed the expression of antiapoptotic proteins (e.g., Bcl‐2, Bcl‐xL), with an observed increase in the quantity of depolarized cells. In addition, the apoptotic effects of picrasidine I were linked to the activation of the c‐Jun N‐terminal kinase and extracellular signal‐regulated kinase pathways and the inhibition of the protein kinase B signaling pathway. A human apoptosis array indicated claspin inhibition upon picrasidine I treatment, suggesting the potential involvement of picrasidine I in apoptosis and cell cycle regulation. Our findings suggest that picrasidine I has potential as a candidate for treating advanced melanoma, and thus these findings warrant further investigation. The modulation of claspin expression by picrasidine I could be investigated further as a potential biomarker to predict its efficacy in related to advanced stages of melanoma.

中文翻译：

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Picrasidine I 通过激活 ERK 和 JNK 通路并抑制 AKT 信号传导来调节黑色素瘤细胞系中的细胞凋亡


世界卫生组织的数据表明黑色素瘤发病率持续增加，转移性黑色素瘤的特点是预后不良和耐药性。探索天然产物衍生的疗法仍然是体外研究的一个活跃领域。本研究的目的是确定 picrasidine I（一种从 Picrasma quassioides 中提取的天然化合物）对两种黑色素瘤细胞系的抗肿瘤作用。我们选择了两种转移性黑色素瘤细胞系 HMY-1 和 A2058 进行分子研究，包括蛋白质印迹、4'，6-二脒基-2-苯基吲哚染色和流式细胞术。Picrasidine I 对 HMY-1 和 A2058 黑色素瘤细胞系具有细胞毒作用。它诱导细胞周期停滞在 sub-G1 期并下调细胞周期相关蛋白 （例如，细胞周期蛋白 A2 、 D1 、细胞周期蛋白依赖性激酶 4 和 6）。在内在细胞凋亡途径中，苦瓜西啶 I 激活促凋亡蛋白 （例如，Bax、Bak、t-Bid、BimL/S） 并抑制抗凋亡蛋白 （例如，Bcl-2、Bcl-xL） 的表达，观察到去极化细胞的数量增加。此外，吡克拉西啶 I 的凋亡作用与 c-Jun N-末端激酶和细胞外信号调节激酶通路的激活以及蛋白激酶 B 信号通路的抑制有关。人细胞凋亡阵列表明 picrasidine I 处理后 claspin 抑制，表明 picrasidine I 可能参与细胞凋亡和细胞周期调节。我们的研究结果表明，吡克拉西定 I 有可能成为治疗晚期黑色素瘤的候选药物，因此这些发现值得进一步研究。 可以进一步研究 picrasidine I 对 claspin 表达的调节，作为预测其在黑色素瘤晚期相关阶段的疗效的潜在生物标志物。