Marsdenia tenacissima Extract Induces Autophagy and Apoptosis of Hepatocellular Cells via MIF/mToR Signaling

Shuai Lin; Qianwen Sheng; Xiaobin Ma; Shanli Li; Peng Xu; Cong Dai; Meng Wang; Huafeng Kang; Zhijun Dai

doi:10.1155/2022/7354700

Marsdenia tenacissima Extract Induces Autophagy and Apoptosis of Hepatocellular Cells via MIF/mToR Signaling

Evid Based Complement Alternat Med. 2022 Mar 4:2022:7354700. doi: 10.1155/2022/7354700. eCollection 2022.

Authors

Shuai Lin¹, Qianwen Sheng², Xiaobin Ma¹, Shanli Li¹, Peng Xu¹, Cong Dai³, Meng Wang¹, Huafeng Kang¹, Zhijun Dai^{1

4}

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
² Department of Oncology, Xi'an International Medical Center Hospital, Xi'an, China.
³ Department of Thyroid Breast Surgery, Xi'an International Medical Center Hospital, Xi'an, China.
⁴ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Abstract

Hepatocellular carcinoma (HCC) seriously endangers humans. In traditional Chinese medicine, Marsdenia tenacissima (MTE) has anti-inflammatory, antiasthmatic, antihypertensive, and anticancer effects. This study reveals the antiproliferative effect of MTE on the HCC cells in vitro and provides a theoretical basis for the development and clinical application of anti-HCC agents. Methods. MHCC-97H and HepG2 cells were cultured in vitro and exposed to various concentrations and durations of MTE, and an MTT assay was used to detect the effects of MTE on cell proliferation. Transmission electron microscopy revealed the morphological changes in the two cell lines after MTE stimulation. The MTE effects on the apoptosis and cell cycle distribution of the cell lines were detected by flow cytometry. Western blotting and qRT-PCR were used to detect target gene expression at the protein and mRNA levels, respectively. Results. MTE reduced the viability of the MHCC-97H and HepG2 cells in a dose- and time-dependent manners (P < 0.05). Autophagic vesicles and apoptotic bodies were found in the MHCC-97H and HepG2 cells after MTE incubation, and the Annexin V-PI assay showed that the apoptotic rates of the cell lines increased with increasing MTE concentration (P < 0.05). Autophagy inducer rapamycin promoted the MTE-induced apoptotic rates of the cell lines, whereas autophagy inhibitor chloroquine inhibited the apoptotic rates. More cells in the S phase were found in the two cell lines after MTE treatment (P < 0.05). After MTE incubation, MIF, CD47, and beclin-1 protein levels significantly increased. Furthermore, in the MTE group, Akt, mTOR, and caspase3 expressions decreased; however, LC 3 expression increased, which was significantly different from the control group (P < 0.05). Conclusions. MTE inhibited proliferation and induced autophagy, apoptosis, and S phase cell cycle arrest in the MHCC-97H and HepG2 cells. These effects might be related to the activation of MIF and mTOR signaling inhibition.