COMMENT Traditional Medicine Research 2021;6(6):50. https://doi.org/10.53388/TMR20211011246 1 Submit a manuscript: https://www.tmrjournals.com/tmr Oriental Medicine Role of oxidative stress in anti-cancer activity of Tripterygium wilfordii Li-Ping Yang 1#* , Jian Hao 2#, , Dan Chen 2 1 Department of Pharmacy, Beijing Hospital; National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing 100730, China. 2 TMR Publishing Group, Auckland 2014, New Zealand. # Li-Ping Yang and Jian Hao are the co-first authors of this paper. *Corresponding to: Li-Ping Yang, Department of Pharmacy, Beijing Hospital; National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), No. 1 Dahua Road, Dongcheng District, Beijing 100730, China. E-mail: yanglp_2000@hotmail.com. Introduction Oxidative stress, a characteristic of tumor cells, is defined as a relative excess of reactive oxygen species (ROS), directly associated with cancer. Although excessive ROS can cause oxidative damage, ROS within a certain threshold range can play an important second messenger function and participate in regulating important signaling pathways in cells, including induction of autophagy and apoptosis. Research has shown that acute and high ROS concentrations can damage DNA and induce cell apoptosis, whereas moderate ROS concentrations can induce temporary or permanent cell cycle arrest and cell differentiation. Chronic and low ROS levels promote cell mitosis and proliferation and increase genomic instability, further leading to tumorigenesis and cancer progression. As cancer cells are less efficient in eliminating ROS and have higher sensitivity to ROS than normal tissues, ROS selectively kill cancer cells. Therefore, the concept of “oxidation-promoting therapy” has been developed. Increasing ROS concentration in the tumor microenvironment could lead to higher cancer inhibition in rats. Tripterygium wilfordii Hook F. (Tripterygium wilfordii) is a plant belonging to the Celastraceae family (Figure 1). It was first recorded in The Classic of Herbal Medicine, a Chinese book on agriculture and medicinal plants, traditionally attributed to Shennong and written approximately between 200 C.E. and 250 C.E. Its root is often used as a medicinal ingredient in the treatment of headache, acute mastitis, and hernias, as well as tubercles or scabies. Since the 1970s, Tripterygium wilfordii has been widely used as an immunosuppressant in clinical practice and has exhibited suitable curative effects in treating autoimmune diseases. The anti-cancer effects of Tripterygium wilfordii have attracted considerable attention among researchers, because many components of Tripterygium wilfordii could directly initiate apoptosis. Triptolide, the most studied ingredient of Tripterygium wilfordii isolated in the 1970s, induces apoptosis in cancer cells such as hepatocellular carcinoma H22 and BEL7402 cells and lung cancer A549 cells. The time-and dose-dependent effects of tripchlorolides on rat ovarian cell apoptosis have also been observed. However, the mechanisms of Tripterygium wilfordii are still under study. Triptolide can increase ROS and induce oxidative stress in the liver and kidney cells. The increase in ROS and depletion of glutathione (GSH) cause lipid peroxidation and DNA damage, eventually leading to hepatic and renal cell damage [1, 2]. Studies on the mitochondrial apoptosis pathway have focused on the role of oxidative stress in the anti-cancer effect of Tripterygium wilfordii. Here, we concentrated on one aspect: the involvement of Tripterygium wilfordii in the induction of oxidative stress, triggering apoptosis in cancer cells. Figure 1 The whole plant and medicinal cite of Tripterygium wilfordii