Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways

Chen-Lin Yu, Institute of Biomedical Science, MacKay Medical College, New Taipei City, Taiwan
Yu-Wei Lai, Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan.
Jih-Jung Chen, Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Jie-Jen Lee, Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
Tsung-Hsien Chou, Public Health Bureau, Pingtung County Government, Pingtung, Taiwan
Chen-Chen Huang, Institute of Biomedical Science, MacKay Medical College, New Taipei City, Taiwan
Shih-Chia Liu, Division of Pediatric Orthopedics, Department of Orthopedic Surgery, MacKay Memorial Hospital, Taipei, Taiwan
Guang-Wei Chen, Department of Chinese Medicine, MacKay Memorial Hospital, Taipei, Taiwan
Chung‐Hsin Tsai, Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
Shih-Wei Wang, Institute of Biomedical Science, MacKay Medical College, New Taipei City, TaiwanFollow

Keywords

Apoptosis, Cryptocaryone, Glycolysis, Hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human HCC cells. In this study, we found that cryptocaryone potently induced growth inhibition by apoptotic cell death in HCC cells. Cryptocaryone also suppressed the ATP synthesis, lactate production and glycolytic capacity of HCC cells. Mechanistic investigations showed that phosphorylation of Akt and c-Src, as well as the expression of HK1 were impeded by cryptocaryone. Moreover, cryptocaryone markedly increased the expression level of transcription factor FoxO1. Importantly, clinical database analysis confirmed the negative correlation between HK1 and FoxO1. High expression levels of HK-1 were positively correlated with poorer survival in patients with HCCs. These results suggest that cryptocaryone may promote cell apoptosis by inhibiting FoxO1-mediated aerobic glycolysis through Akt and c-Src signaling cascades in human HCC cells. This is the first study to indicate that cryptocaryone exerts anti-cancer property against human HCC cells. Cryptocaryone is a potential natural product worthy of further development into a promising candidate for HCC treatment.

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Recommended Citation

Yu, Chen-Lin; Lai, Yu-Wei; Chen, Jih-Jung; Lee, Jie-Jen; Chou, Tsung-Hsien; Huang, Chen-Chen; Liu, Shih-Chia; Chen, Guang-Wei; Tsai, Chung‐Hsin; and Wang, Shih-Wei (2023) "Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways," Journal of Food and Drug Analysis: Vol. 31 : Iss. 4 , Article 10.
Available at: https://doi.org/10.38212/2224-6614.3480