Emodin induces apoptosis and suppresses non-small-cell lung cancer growth via downregulation of sPLA2-IIa

• Published in: Phytomedicine (Stuttgart) Vol. 95; p. 153786
• Main Authors: Zhang, Fang-Yuan, Li, Run-Ze, Xu, Cong, Fan, Xing-Xing, Li, Jia-Xin, Meng, Wei-Yu, Wang, Xuan-Run, Liang, Tu-Liang, Guan, Xiao-Xiang, Pan, Hu-Dan, Liu, Liang, Yao, Xiao-Jun, Wu, Qi Biao, Leung, Elaine Lai-Han
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01-01-2022
• Subjects: Apoptosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Down-Regulation; Emodin; Emodin - pharmacology; Humans; Lung Neoplasms - drug therapy; NSCLC; Phospholipases A2, Secretory; sPLA2-IIa; TCM; AA; ACC; AdPLA2; SCLC; sPLA2-IIa; NSCLC; IRS1; NF-kB; cPLA2; PLA2; PFA; Emodin; ROS; AMPK; sPLA2; iPLA2; TCM
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2021.153786

•SPLA2-IIa was always overexpressed in cancers and played important role in cancer development.•Emodin could inhibit NSCLC cell proliferation through down-regulating the expression level of sPLA2-IIa.•Emodin could induce the apoptosis, increase the ROS level, and arrest the cell cycle at G2/M phase.
Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development.
This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC).
MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model.
Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle.
Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.
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