P2Et extract obtained from the Caesalpinia spinosa plant is abundant in phenolic compounds such as gallic acid and ethyl gallate and can generate signals to activate the immune response by inducing a mechanism known as immunogenic cell death in murine models of breast cancer and melanoma. Immunogenic cell death involves mechanisms such as autophagy, which can be modulated by various natural compounds, including phenolic compounds with a structure similar to those found in P2Et extract. Here, we determine the role of autophagy in apoptosis and the generation of immunogenic signals using murine wild-type B16-F10 melanoma cells and cells with beclin-1 gene knockout. We show that P2Et extract and ethyl gallate induced autophagy, partially protecting tumor cells from death and promoting calreticulin exposure and the release of ATP. Although ethyl gallate showed a mechanism similar to that of P2Et, the induction of apoptosis and immunogenic signals was significantly weaker. In contrast, gallic acid-induced autophagy acted by blocking autophagic flux, which was associated with increased cell death. However, this compound did not induce any of the immunogenic death signals evaluated. Therefore, the complex extract has greater antitumor potential than isolated compounds. Here, we show that inducing autophagic flux with P2Et protects cancer cells from cell death and that this delay in cell death is required for the generation of immunogenic signals.

从所获得的提取物P2Et刺云实植物富含酚类化合物，例如没食子酸和没食子酸乙酯，并且可以通过在乳腺癌和黑色素瘤小鼠模型中诱导称为免疫原性细胞死亡的机制来产生激活免疫反应的信号。免疫原性细胞死亡涉及自噬等机制，可通过各种天然化合物进行调节，包括结构类似于 P2Et 提取物中的酚类化合物。在这里，我们使用鼠野生型 B16-F10 黑色素瘤细胞和具有 beclin-1 基因敲除的细胞确定自噬在细胞凋亡和免疫原性信号产生中的作用。我们表明 P2Et 提取物和没食子酸乙酯诱导自噬，部分保护肿瘤细胞免于死亡并促进钙网蛋白暴露和 ATP 的释放。尽管没食子酸乙酯表现出与 P2Et 相似的机制，细胞凋亡和免疫原性信号的诱导明显较弱。相比之下，没食子酸诱导的自噬通过阻断自噬通量起作用，这与细胞死亡增加有关。然而，该化合物不诱导任何评估的免疫原性死亡信号。因此，复合提取物比分离的化合物具有更大的抗肿瘤潜力。在这里，我们表明用 P2Et 诱导自噬流可以保护癌细胞免于细胞死亡，并且这种细胞死亡的延迟是产生免疫原性信号所必需的。复合提取物比分离的化合物具有更大的抗肿瘤潜力。在这里，我们表明用 P2Et 诱导自噬流可以保护癌细胞免于细胞死亡，并且这种细胞死亡的延迟是产生免疫原性信号所必需的。复合提取物比分离的化合物具有更大的抗肿瘤潜力。在这里，我们表明用 P2Et 诱导自噬流可以保护癌细胞免于细胞死亡，并且这种细胞死亡的延迟是产生免疫原性信号所必需的。