Asiatic Acid Induces Mitochondrial Apoptosis via Inhibition of JAK2/STAT3 Signalling Pathway in Human Osteosarcoma

Yan, B. F.; Chen, X.; Liu, J.; Liu, S. J.; Zhang, J. Z.; Zeng, Qingqi; Duan, J. A.

doi:10.14712/fb2021067030108

Folia Biologica > Archive > 2021, Vol. 67 > Issue 3 > Asiatic Acid Induces Mitochondrial…

Fol. Biol. 2021, 67, 108-117

https://doi.org/10.14712/fb2021067030108

Asiatic Acid Induces Mitochondrial Apoptosis via Inhibition of JAK2/STAT3 Signalling Pathway in Human Osteosarcoma

B. F. Yan^1,2, X. Chen³, J. Liu², S. J. Liu¹, J. Z. Zhang², Qingqi Zeng², J. A. Duan¹

¹Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine; Nanjing, China
²Jiangsu Health Vocational College; Nanjing, China
³Jiangsu College of Nursing; Huaian, China

Received May 2021
Accepted June 2021

Osteosarcoma (OS), a severe malignant bone tumour, usually occurs in adolescents and children and has a poor prognosis. Asiatic acid (AA), an active component isolated from Centella asiatica (L.) Urb., exhibits appreciable anti-oxidant and anti-tumour activities. So far, the effects and underlying mechanisms of AA against OS have not been clarified. Here, we explored the anti-tumour effects of AA against human OS and the involved mechanism mediating its actions. To evaluate effects of AA on the cell proliferation of human OS cells, cell viability and colony formation assays were performed. Flow cytometry was used to evaluate apoptosis in OS cells exposed to AA and mitochondrial membrane potential. Western blotting and RT-PCR were applied to determine expression of the relevant proteins and their mRNA levels. Our explorations showed that AA inhibits proliferation of human OS cells in a concentration- and time-dependent manner, and induces apoptosis of OS cells by the intrinsic (mitochondrial) pathway. Importantly, we found that inhibition of the AA-induced phosphorylation of JAK2/STAT3 signalling molecules and the decrease in MCL-1 contributed to the anti-tumour efficacy of AA. Collectively, our results suggest that AA could evoke mitochondrial- induced apoptosis in human OS cells by suppression of the JAK2/STAT3 pathway and MCL-1 expression. These results strongly demonstrate that AA could be a potential anti-tumour agent for OS treatment.

Keywords

osteosarcoma, asiatic acid, mitochondrial apoptosis, JAK2/STAT3/MCL-1.

Funding

This work was supported by the Natural Science Foundation of Jiangsu Province (BK20191498), Project of State Administration of Chinese Medicine (NZYJDMF-2020001), Medical Scientific Research Project of Jiangsu Provincial Health Commission (ZDB2020020) and university-level project of Jiangsu Health Vocational College (JKA201916).