Direct cellular targets and anticancer mechanisms of the natural product oridonin

Abstract

Cancer 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 antiinflammatory, 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.

Oridonin: A Mini Review on the Anti-Cancer, Anti-Inflammatory, Cardioprotective, Hepatoprotective, Renoprotective and Lung Protective Properties

“…13,14 ORI and its analogs have been shown to exhibit potent anti-cancer activities by promoting apoptosis, inducing cell cycle arrest, inhibiting angiogenesis and suppressing metastasis in a broad spectrum of cancer types. 15 ORI is therefore a multi-functional anti-cancer compound that modulates a network of cancer related targets and signaling pathways. Other pharmacological properties of ORI and its derivatives are antiinflammatory, anti-neuroinflammatory, anti-bacterial, cardioprotective, neuroprotective, hepatorenal protective, lung protective and osteoblast protective activities.…”