Ki Yo Sook, Chung Kyung-Sook, Lee Heon-Woo, Choi Jung-Hye, Tapondjou Léon Azefack, Jang Eungyeong, Lee Kyung-Tae
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Korea.
Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Korea.
Pharmaceuticals (Basel). 2022 Jul 19;15(7):893. doi: 10.3390/ph15070893.
In our previous study, we reported the isolation of pennogenin-3--α--rhamnopyranosyl-(1→2)-[α--rhamnopyranosyl-(1→3)]-β--glucopyranoside (spiroconazol A), a steroidal saponin, from the flowers of L. var. . In the present study, we aimed to investigate the effects of spiroconazol A on autophagy and its underlying mechanisms in A549 and NCI-H358 human non-small cell lung cancer (NSCLC) cells. Spiroconazol A inhibited the proliferation of NSCLC cells in a concentration- and time-dependent manner. To determine the type of programmed cell death induced by spiroconazol A, we performed a characterization of apoptosis in spiroconazol A-treated A549 cells. Our results showed that spiroconazol A significantly suppressed A549 cell viability but did not influence cell apoptosis because phosphatidylserine and caspase activation were not detected. Furthermore, spiroconazol A treatment upregulated the expression of LC3-II and autophagy-related Beclin-1 protein, suggesting that spiroconazol A induces autophagy in A549 cells. Moreover, spiroconazol A activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) but did not affect the phosphorylation of Janus kinase or ERK1/2. Notably, SB203580, a p38 MAPK inhibitor, had a significant inhibitory effect on spiroconazol A-induced autophagic cell death in A549 cells. Our results indicated that spiroconazol A-induced autophagy is dependent on p38 MAPK signaling and has potential as a therapeutic target in NSCLC.
在我们之前的研究中，我们报道了从长柱开口箭（Tupistra grandistigma (Wang et Lo) Wang et S. C. Chen var. longistyla Hand.-Mazz.）的花中分离出了甾体皂苷原薯蓣皂苷元-3-α-鼠李吡喃糖基-(1→2)-[α-鼠李吡喃糖基-(1→3)]-β-葡萄糖吡喃糖苷（螺旋贝母皂苷A）。在本研究中，我们旨在研究螺旋贝母皂苷A对A549和NCI-H358人非小细胞肺癌（NSCLC）细胞自噬的影响及其潜在机制。螺旋贝母皂苷A以浓度和时间依赖性方式抑制NSCLC细胞的增殖。为了确定螺旋贝母皂苷A诱导的程序性细胞死亡类型，我们对经螺旋贝母皂苷A处理的A549细胞进行了凋亡特征分析。我们的结果表明，螺旋贝母皂苷A显著抑制A549细胞活力，但未影响细胞凋亡，因为未检测到磷脂酰丝氨酸和半胱天冬酶激活。此外，螺旋贝母皂苷A处理上调了LC3-II和自噬相关Beclin-1蛋白的表达，表明螺旋贝母皂苷A在A549细胞中诱导自噬。此外，螺旋贝母皂苷A激活了p38丝裂原活化蛋白激酶（MAPK）的磷酸化，但不影响Janus激酶或ERK1/2的磷酸化。值得注意的是，p38 MAPK抑制剂SB203580对螺旋贝母皂苷A诱导的A549细胞自噬性细胞死亡具有显著抑制作用。我们的结果表明，螺旋贝母皂苷A诱导的自噬依赖于p38 MAPK信号传导，并且在NSCLC中具有作为治疗靶点的潜力。
