Artemisinin potentiates apoptosis and triggers cell cycle arrest to attenuate malignant growth of salivary gland tumor cells

Peng  Xiao; Qiujuan  Liang; Qiuqiu  Chen; Haixia Liu

doi:10.18388/abp.2020_5845

Peng Xiao Department of Stomatology, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi 830028, Xinjiang, China
Qiujuan Liang Department of Stomatology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, Xinjiang, China
Qiuqiu Chen Department of Stomatology, The Second Affiliated Hospital of Zhejiang University of Chinese Medicine, Hangzhou 310005, Zhejiang, China
Haixia Liu Department of Stomatology, Yangpu District Central Hospital of Shanghai (Yangpu Hospital Affiliated From Tongji University), Shanghai 200090, China

DOI: https://doi.org/10.18388/abp.2020_5845

Abstract

One of the rare malignant tumors developing within the glands of the buccal cavity in human beings is salivary gland tumors (SGTs). The hallmark of SGTs is the fusion of nuclear factor IB (NFIB) and myeloblastosis (MYB) genes developed after the translocation of q22-23; p23-24. Although the aetiology of SGTs is not clear, however, the therapeutic modalities are surgical resection followed by the combination of chemotherapy and radiotherapy if a chance of recurrence seems to develop. Owing to have numerous side effects of chemotherapy, the drug development has been shifted to natural products with minimal side effects. One of the key phytochemical artemisinin derived from wormwood Artemisia annua exhibits various pharmacological activities against various in-vivo and in-vitro cellular models. Here, we evaluated the cytotoxic potential of artemisinin against A-253 cells with possible underlying cell death mechanisms. Our results showed that artemisinin reduces the proliferation of cells in a concentration-dependent manner and displays IC50 value in a range of 10.23, 14.21 μM, and 203.18 μM against A-253/HTB-41 and transformed salivary gland SMIE cells, respectively. Flow cytometry analysis demonstrated that artemisinin promotes a significant amount of apoptotic cellular population and triggers G0/G1 arrest of A-253 cells in a concentration-dependent manner. To verify the mechanism of cell death induced by artemisinin in A-253 cells, we found an increased level of Bax, Bim, Bad, Bak and reduced level of antiapoptotic protein Bcl-2, Bcl-XL with concomitant release of mitochondrial resident protein cytochrome c into the cytoplasm. Additionally, we found that artemisinin augments the production of reactive oxygen species which further leads to the activation of proapoptotic proteins PARP1, and caspase-3, in a concentration-dependent manner thereby triggering apoptosis. In conclusion, artemisinin exhibits promising anticancer therapeutic potential against A-253 cells and needs further validation of in-vitro results in preclinical models.