Affiliation:
1. Department of Clinical Pharmacology, College of Pharmacy Dalian Medical University Dalian China
2. TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine Chengdu University of Traditional Chinese Medicine Chengdu China
3. College of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu China
4. Department of Pathology, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital Sichuan University, and Collaborative Innovation Chengdu China
Abstract
AbstractCancer is one of the leading causes of death worldwide. The proliferation, survival, and metastasis of cancer cells are governed by a complex series of intracellular and extracellular signaling pathways. Therefore, efficient cancer therapy often requires the modulation of multiple targets. Besides, the modulation of several biological targets with a single drug can lead to synergistic therapeutic effects and avoid side effects associated with combination therapy. Oridonin, an ent‐kaurane type diterpenoid isolated from Rabdosia rubescens, has been reported to possess potent anti‐inflammatory, antioxidant, anticancer, and neuroprotective activities. Among its many benefits, the anticancer effects have attracted the most attention because of its effectiveness in many tumor cells and its potential to overcome therapeutic resistance. Recently, several proteins involved in oncogenic signaling, including CRM1, PHGDH, HSP70, AML1‐ETO, and STAT3, were identified as functional targets of oridonin and its analogs. The binding mechanism and the consequence of oridonin binding to these oncogenic proteins are summarized and discussed. These advances suggest that oridonin exhibits broad spectrum anticancer effects by targeting multiple oncogenic proteins mainly via Michael addition between its unsaturated ketone and the cysteines in the target proteins. Therefore, oridonin and its derivatives hold the potential to be developed as multitargeting anticancer drugs.
Funder
Chengdu University of Traditional Chinese Medicine