alkaloid, induced apoptosis of human myeloid leukemia cells by upregulating proapoptotic proteins and downregulating cyclins (8). Matrine, an alkaloid derived from the Sophora flave‐ scensait, promoted apoptosis of gastric cancer cells by boosting

Gastric cancer is a common malignancy in China, with the second highest mortality rate worldwide. Advanced gastric cancer usually exhibits a poor prognosis with a low 5‐year survival rate. Therefore, developing novel drugs for the treatment of this cancer will be beneficial for patients. Demethylzeylasteral, an extract of tripterygium wilfordii, has shown positive anticancer activities. However, the possible antitumor effect of demethylzeylasteral on gastric cancer cells and its underlying molecular mechanism remain to be determined. In the present study, the Cell Counting Kit‐8 and colony formation assays revealed that demeth‐ ylzeylasteral impeded the proliferation of human gastric cancer cells in a dose‐dependent manner. Furthermore, the Transwell assay identified an inhibitory effect of demeth‐ ylzeylasteral on the migration of MKN‐45 cells, while flow cytometry found that treatment with demethylzeylas‐ teral induced apoptosis and decreased the mitochondrial membrane potential in the cancer cells. Further investiga‐ tion revealed that demethylzeylasteral downregulated the phosphorylation of ERK1/2, AKT, and GSK‐3β in MKN‐45 cells. Notably, decreased expression of Bcl‐2 and increased expression of Bax, cleaved caspase‐3, cleaved caspase‐9 and cleaved PARP were detected in the cancer cells treated with demethylzeylasteral. The present study demonstrated that demethylzeylasteral exhibits therapeutic potential for gastric cancer. Introduction The global burden of cancer continues to increase due to a variety of factors (1). Gastric cancer is the fourth most common cancer worldwide and is the second most common cause of cancer‐associated mortality (2). The treatment of gastric cancer includes surgery, chemotherapy, radiotherapy and molecular targeted therapy, among which surgery combined with chemo‐ radiotherapy is the most effective treatment regimen (3). However, the treatment has entered a bottleneck period due to congenital or acquired drug resistance and postoperative recurrence (4). Therefore, identification of new targets and signaling pathways related to the progression of gastric cancer may be beneficial for the treatment of gastric cancer. Tumor occurrence and development are closely associated with uncontrolled cell proliferation, while malignant cells often escape apoptosis to obtain unlimited proliferation capacity (5). In this case, three types of evasion mechanisms of apoptosis exist, including the weakening of caspase function, the damage of the death receptor pathway, and the destruction of the balance between anti‐apoptotic and pro‐apoptotic proteins (6). Therefore, targeting cancer cell apoptosis by modulating key proteins or enzymes in the apoptosis‐related signaling pathway has become an area of focus in cancer research (7). Notably, a number of natural products have been shown to act in apoptosis signaling pathways involved in cancer cell death. Camptothecin, a quino‐ line alkaloid, induced apoptosis of human myeloid leukemia cells by upregulating proapoptotic proteins and downregulating cyclins (8). Matrine, an alkaloid derived from the Sophora flave‐ scensait, promoted apoptosis of gastric cancer cells by boosting the pro‐apoptotic proteins, altering the ratio of Fas/FasL and activating caspase‐3 (9,10). These findings have led researchers to focus on developing new potential anticancer agents. Demethylzeylasteral is a triterpene monomer extracted from tripterygium wilfordii, which has been widely used in the study of anti‐inflammatory immune regulation, antifertility and estrogen metabolism regulation (11‐14). In recent years, the anticancer properties of demethylzeylasteral have been continuously studied. Li et al (15) reported that demethylzey‐ lasteral significantly impeded the invasion of triple‐negative breast cancer by blocking the TGF‐β signaling pathway (15). Meanwhile, this compound may suppress glioma growth by mediating the miR‐30e‐5p/MYBL2 axis (16). Notably, Identification of an antitumor effect of demethylzeylasteral on human gastric cancer cells YANG YANG, MENGLIN ZHAO, TING HU, FANG SU, FENG QIAN and ZISHU WANG Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China Received March 24, 2020; Accepted September 7, 2020 DOI: 10.3892/ol.2020.12310 Correspondence to: Professor Zishu Wang or Professor Feng Qian, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui 233004, P.R. China E‐mail: wzshahbb@163.com E‐mail: fengqian@sjtu.edu.cn