Solasodine inhibited the proliferation of gastric cancer cells through suppression of Hedgehog/Gli1 signaling

IF 3.1 3区农林科学 Q3 FOOD SCIENCE & TECHNOLOGY

Food Science and Biotechnology Pub Date : 2025-07-19 DOI:10.1007/s10068-025-01946-4

Yimeng Zhou, Jin Tae Kim, Xiaoman Zhan, Alina Ghimire, Kang Hyuk Lee, Hui Mang Son, Hong Jin Lee

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Abstract

In this study, we investigated the beneficial effect of solasodine, a steroidal alkaloid from Solanaceae plants, on suppressing the proliferation of gastric cancer cells by targeting Hedgehog (Hh) signaling. Solasodine inhibited the proliferation of AGS and MKN74 gastric cancer cells and regulated cell cycle (Cyclin D1 and p27) and apoptosis (Bax and Bcl-2) markers in a dose-dependent manner, consistent with the Gli1/2 inhibitor Gant61 but not the Smo inhibitor vismodegib. As an upstream regulator, solasodine inhibited Hh signaling by down-regulating Gli1 expression and blocking its nuclear localization without affecting Smo levels. Molecular docking revealed stable binding of solasodine to Gli1, with a binding affinity of −7.4 kcal/mol. Moreover, solasodine inhibited Gli1 rather than Smo expression in Hh signaling overexpressed Ptch (−/−) MEF cells. Our findings demonstrate that solasodine inhibits gastric cancer proliferation by targeting Hh/Gli1 signaling, underscoring its potential as a potent agent for prevention and/or inhibition of gastric cancer.

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Solasodine通过抑制Hedgehog/Gli1信号传导抑制胃癌细胞增殖

在本研究中，我们研究了来自茄科植物的甾体生物碱solasodine通过靶向Hedgehog （Hh）信号抑制胃癌细胞增殖的有益作用。索拉索定抑制胃癌AGS和MKN74细胞的增殖，并以剂量依赖的方式调节细胞周期（Cyclin D1和p27）和凋亡（Bax和Bcl-2）标志物，与Gli1/2抑制剂Gant61一致，但与Smo抑制剂vismodegib不一致。作为上游调节剂，solasodine通过下调Gli1表达并阻断其核定位而不影响Smo水平，从而抑制Hh信号传导。分子对接表明，solasodine与Gli1的结合稳定，结合亲和力为−7.4 kcal/mol。此外，solasodine在Hh信号过表达的Ptch(−/−)MEF细胞中抑制Gli1而不是Smo的表达。我们的研究结果表明，solasodine通过靶向Hh/Gli1信号传导抑制胃癌增殖，强调其作为预防和/或抑制胃癌的有效药物的潜力。

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来源期刊

Food Science and Biotechnology FOOD SCIENCE & TECHNOLOGY-

CiteScore

5.40

自引率

3.40%

发文量

174

审稿时长

2.3 months

期刊介绍： The FSB journal covers food chemistry and analysis for compositional and physiological activity changes, food hygiene and toxicology, food microbiology and biotechnology, and food engineering involved in during and after food processing through physical, chemical, and biological ways. Consumer perception and sensory evaluation on processed foods are accepted only when they are relevant to the laboratory research work. As a general rule, manuscripts dealing with analysis and efficacy of extracts from natural resources prior to the processing or without any related food processing may not be considered within the scope of the journal. The FSB journal does not deal with only local interest and a lack of significant scientific merit. The main scope of our journal is seeking for human health and wellness through constructive works and new findings in food science and biotechnology field.