甘波酸（GA）是由Garcinia hanburyi树分泌的一种天然黄酮类化合物。它在各种癌症类型中具有抗癌活性。在胃癌中，它通过增加凋亡来抑制细胞增殖。然而，甘波酸诱导的胃癌增殖抑制是否涉及坏死凋亡仍不清楚。在本研究中，我们发现RIPK1特异性抑制剂坏死素1（Nec-1）减轻了甘波酸引起的增殖抑制作用。甘波酸处理增加了坏死凋亡相关蛋白RIPK1、RIPK3和MLKL的磷酸化，并促使它们相互作用形成坏死体复合物。效应蛋白Drp-1在甘波酸处理中发生了脱磷酸化。使用不同的坏死凋亡抑制剂和PGAM5沉默能减轻甘波酸诱导的胃癌细胞株的细胞死亡，从而减轻甘波酸引起的细胞增殖抑制。所有数据支持甘波酸通过诱导坏死凋亡来抑制胃癌细胞增殖的结论。Copyright © 2023 Shujun Wang et al.

Gambogic acid (GA) is a natural xanthonoid secreted by Garcinia hanburyi tree. It possesses anti-cancer activity in various types of cancers. In gastric cancer, it inhibits cell proliferation through increasing apoptosis. However, whether necroptosis is involved in the GA-induced proliferation inhibited in gastric cancer is unknown. In the present study, we found that RIPK1 specific inhibitor necrostatin-1 (Nec-1) attenuated GA-induced proliferation inhibition. GA treatment increased the phosphorylation of necroptosis-related proteins, RIPK1, RIPK3, and MLKL, and their interactions to form the necrosome complex. The effector protein Drp-1 was dephosphorylated by GA treatment. Inhibition of necroptosis by different inhibitors and PGAM5 knockdown attenuated GA-induced cell death in gastric cancer cell lines, thereby attenuating GA-caused cell proliferation inhibition. All the data supported the conclusion that GA could inhibit gastric cancer cell proliferation by inducing necroptosis.Copyright © 2023 Shujun Wang et al.