Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition

Li Wang; Yongjun Wang; Zexu Wang; Xiuwei Zhang; Huayong Chen; Qiuqi Lin; Xin Wang; Yuting Wen; Xia Pan; Zhongliang Guo; Bing Wan

doi:10.1016/j.heliyon.2024.e29447

Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition

Heliyon. 2024 Apr 9;10(8):e29447. doi: 10.1016/j.heliyon.2024.e29447. eCollection 2024 Apr 30.

Authors

Li Wang¹, Yongjun Wang¹, Zexu Wang¹, Xiuwei Zhang¹, Huayong Chen², Qiuqi Lin¹, Xin Wang¹, Yuting Wen¹, Xia Pan¹, Zhongliang Guo³, Bing Wan¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, China.
² Lanshan Central Hospital, Yongzhou, Hunan, 425899, China.
³ Department of Respiratory and Critical Care Medicine, The Affiliated Shanghai East Hospital of Nanjing Medical University, Shanghai, 200120, China.

Abstract

Objective: Grifolin is a natural secondary metabolite isolated from edible fruiting bodies of the mushroom Albatrellus confluens. Grifolin has antitumor activities in several types of cancer. We aimed to determine the effects of grifolin on lung cancer.

Methods: We determined the proliferation, migration, invasion, and apoptosis of lung cancer cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Ethynyl deoxyuridine, colony formation, wound scratch, transwell, flow cytometry, and xenograft mouse assays. Molecular docking evaluated the binding relation between grifolin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). The levels of PIK3CA, AKT, and p-AKT were measured by western blot.

Results: Grifolin (10, 20, or 40 μM) inhibited the proliferation, migration, and invasion of lung cancer cells, and induced cell cycle arrest and apoptosis. Grifolin also decreased CDK4, CDK6, and CyclinD1 expression and significantly decreased PIK3CA and p-AKT expression in lung cancer cells. These anticancer effects were abolished by 740Y-P.

Conclusions: Grifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.

Keywords: Grifolin; Lung cancer; PI3K/AKT.