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20(S)‐protopanaxadiol ginsenosides induced cytotoxicity via blockade of autophagic flux in HGC‐27 cells
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-06-29 , DOI: 10.1002/cbdv.202000187 Qingqing Han 1 , Lijuan Han 2 , Fangfang Tie 3 , Zhenhua Wang 1 , Chengjun Ma 1 , Ji Li 1 , Honglun Wang 1, 3 , Gang Li 1
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-06-29 , DOI: 10.1002/cbdv.202000187 Qingqing Han 1 , Lijuan Han 2 , Fangfang Tie 3 , Zhenhua Wang 1 , Chengjun Ma 1 , Ji Li 1 , Honglun Wang 1, 3 , Gang Li 1
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(20S)‐Protopanaxadiol ginsenosides Rg3, Rh2 and PPD have been demonstrated for their anticancer activity. However, the underlying mechanism of their antitumor activity remains unclear. In the present study, we investigated the role of these three ginsenosides on cell proliferation and death of human gastric cancer cells (HGC‐27 cells). The sulforhodamine B (SRB) assay, Western blot analysis, fluorescence microscopy, confocal microscopy, high performance liquid chromatography (HPLC) analysis, flow cytometry, and transmission electron microscopy (TEM) were used to evaluate cell proliferation, apoptosis, and autophagy. The results showed that both Rh2 and PPD were more effective than Rg3 in inhibiting HGC‐27 cell proliferation and inducing cytoplasmic vacuolation, while no significant changes in apoptosis were observed. Interestingly, cytoplasmic vacuolation and blockade of autophagy flux were observed after treatment with Rh2 and PPD. Rh2 obviously up‐regulated the expression of the LC3II and p62. Furthermore, the increase in lysosomal pH and membrane rupture was observed in Rh2‐treated and PPD‐treated cells. When HGC‐27 cells were pretreated with bafilomycin A1, a specific inhibitor of endosomal acidification, cellular vacuolization was increased, and the cell viability was significantly decreased, which indicated that Rh2‐induced lysosome‐damage accelerated cell death. Furthermore, data derived from mitochondrial analysis showed that excessive mitochondrial reactive oxygen species (ROS) and dysregulation of mitochondrial energy metabolism were caused by Rh2 and PPD treatment in HGC‐27 cells. Taken together, these phenomena indicated that Rh2 and PPD inhibited HCG‐27 cells proliferation by inducing mitochondria damage, dysfunction of lysosomes, and blockade of autophagy flux. The number of glycosyl groups at C‐3 position could have an important effect on the cytotoxicity of Rg3, Rh2 and PPD.
中文翻译：
20(S)-protopanaxadiol ginsenosides 通过阻断 HGC-27 细胞中的自噬流诱导细胞毒性
(20S)-Protopanaxadiol ginsenosides Rg3、Rh2 和 PPD 已被证明具有抗癌活性。然而，其抗肿瘤活性的潜在机制仍不清楚。在本研究中，我们研究了这三种人参皂苷对人胃癌细胞（HGC-27 细胞）细胞增殖和死亡的作用。磺罗丹明 B (SRB) 测定、蛋白质印迹分析、荧光显微镜、共聚焦显微镜、高效液相色谱 (HPLC) 分析、流式细胞术和透射电子显微镜 (TEM) 用于评估细胞增殖、凋亡和自噬。结果表明，Rh2和PPD在抑制HGC-27细胞增殖和诱导细胞质空泡化方面均比Rg3更有效，但未观察到细胞凋亡的显着变化。有趣的是，在用 Rh2 和 PPD 处理后观察到细胞质空泡化和自噬通量的阻断。Rh2 明显上调 LC3II 和 p62 的表达。此外，在 Rh2 处理和 PPD 处理的细胞中观察到溶酶体 pH 值和膜破裂的增加。当 HGC-27 细胞用内体酸化的特异性抑制剂巴弗洛霉素 A1 预处理时，细胞空泡化增加，细胞活力显着降低，这表明 Rh2 诱导的溶酶体损伤加速了细胞死亡。此外，来自线粒体分析的数据表明，在 HGC-27 细胞中，Rh2 和 PPD 处理会导致过量的线粒体活性氧 (ROS) 和线粒体能量代谢失调。综合起来，这些现象表明 Rh2 和 PPD 通过诱导线粒体损伤、溶酶体功能障碍和自噬通量阻断来抑制 HCG-27 细胞增殖。C-3 位糖基的数量可能对 Rg3、Rh2 和 PPD 的细胞毒性有重要影响。
更新日期：2020-06-29
中文翻译：
20(S)-protopanaxadiol ginsenosides 通过阻断 HGC-27 细胞中的自噬流诱导细胞毒性
(20S)-Protopanaxadiol ginsenosides Rg3、Rh2 和 PPD 已被证明具有抗癌活性。然而，其抗肿瘤活性的潜在机制仍不清楚。在本研究中，我们研究了这三种人参皂苷对人胃癌细胞（HGC-27 细胞）细胞增殖和死亡的作用。磺罗丹明 B (SRB) 测定、蛋白质印迹分析、荧光显微镜、共聚焦显微镜、高效液相色谱 (HPLC) 分析、流式细胞术和透射电子显微镜 (TEM) 用于评估细胞增殖、凋亡和自噬。结果表明，Rh2和PPD在抑制HGC-27细胞增殖和诱导细胞质空泡化方面均比Rg3更有效，但未观察到细胞凋亡的显着变化。有趣的是，在用 Rh2 和 PPD 处理后观察到细胞质空泡化和自噬通量的阻断。Rh2 明显上调 LC3II 和 p62 的表达。此外，在 Rh2 处理和 PPD 处理的细胞中观察到溶酶体 pH 值和膜破裂的增加。当 HGC-27 细胞用内体酸化的特异性抑制剂巴弗洛霉素 A1 预处理时，细胞空泡化增加，细胞活力显着降低，这表明 Rh2 诱导的溶酶体损伤加速了细胞死亡。此外，来自线粒体分析的数据表明，在 HGC-27 细胞中，Rh2 和 PPD 处理会导致过量的线粒体活性氧 (ROS) 和线粒体能量代谢失调。综合起来，这些现象表明 Rh2 和 PPD 通过诱导线粒体损伤、溶酶体功能障碍和自噬通量阻断来抑制 HCG-27 细胞增殖。C-3 位糖基的数量可能对 Rg3、Rh2 和 PPD 的细胞毒性有重要影响。
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