Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells

Jun Ma; Zhaohai Pan; Hongchao Du; Xiaojie Chen; Xuejie Zhu; Wenjin Hao; Qiusheng Zheng; Xuexi Tang

doi:10.3892/ol.2023.13913

Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells

Oncol Lett. 2023 Jun 13;26(2):327. doi: 10.3892/ol.2023.13913. eCollection 2023 Aug.

Authors

Jun Ma^{1

2}, Zhaohai Pan², Hongchao Du³, Xiaojie Chen², Xuejie Zhu², Wenjin Hao⁴, Qiusheng Zheng^{2

5}, Xuexi Tang¹

Affiliations

¹ College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266003, P.R. China.
² Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
³ Department of General Surgery, Binzhou Medical University Affiliated Yantai Yeda Hospital, Yantai, Shandong 265599, P.R. China.
⁴ School of Life Sciences, Nantong University, Nantong, Jiangsu 226019, P.R. China.
⁵ Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Shihezi University, Shihezi, Xinjiang 832099, P.R. China.

Abstract

Gastric cancer is one of the most lethal cancers worldwide. Research has focused on exploring natural medicines to improve the systematic chemotherapy for gastric cancer. Luteolin, a natural flavonoid, possesses anticancer activities. Nevertheless, the mechanism of the anticancer effects of luteolin is still not clear. The present study aimed to verify the inhibitory effect of luteolin on gastric cancer HGC-27, MFC and MKN-45 cells and to explore the underlying mechanism. A Cell Counting Kit-8 cell viability assay, flow cytometry, western blot, an ATP content assay and an enzyme activity testing assay were used. Luteolin inhibited the proliferation of gastric cancer HGC-27, MFC and MKN-45 cells. Further, it impaired mitochondrial integrity and function by destroying the mitochondrial membrane potential, downregulating the activities of mitochondrial electron transport chain complexes (mainly complexes I, III and V), and unbalancing the expression of B cell lymphoma-2 family member proteins, eventually leading to apoptosis of gastric cancer HGC-27, MFC and MKN-45 cells. The intrinsic apoptosis pathway was involved in luteolin's anti-gastric cancer effects. Furthermore, mitochondria were the main target in luteolin-induced gastric cancer apoptosis. The present study may provide a theoretical basis for the research on the effect of luteolin on the mitochondrial metabolism in cancer cells, and pave the way for its practical application in the future.

Keywords: B cell lymphoma-2 family; apoptosis; gastric cancer cell; luteolin; mitochondria; mitochondrial electron transport chain.

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant no. 31471338), the Key Research and Development Program of Shandong Province of China (grant no. 2019GSF108214) and the Natural Science Foundation of Shandong Province (grant no. ZR2016HB51).