Mechanistic Pathways and Molecular Targets of Plant-Derived Anticancer -Kaurane Diterpenes

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2020 Jan 23

PMID 31963204

Citations 25

Authors

Md Shahid Sarwar

Yi-Xuan Xia

Zheng-Ming Liang

Siu Wai Tsang

Hong-Jie Zhang

Affiliations

Soon will be listed here.

Abstract

Since the first discovery in 1961, more than 1300 -kaurane diterpenoids have been isolated and identified from different plant sources, mainly the genus . Chemically, they consist of a perhydrophenanthrene subunit and a cyclopentane ring. A large number of reports describe the anticancer potential and mechanism of action of -kaurane compounds in a series of cancer cell lines. Oridonin is one of the prime anticancer -kaurane diterpenoids that is currently in a phase-I clinical trial in China. In this review, we have extensively summarized the anticancer activities of -kaurane diterpenoids according to their plant sources, mechanistic pathways, and biological targets. Literature analysis found that anticancer effect of -kauranes are mainly mediated through regulation of apoptosis, cell cycle arrest, autophagy, and metastasis. Induction of apoptosis is associated with modulation of BCL-2, BAX, PARP, cytochrome c, and cleaved caspase-3, -8, and -9, while cell cycle arrest is controlled by cyclin D1, c-Myc, p21, p53, and CDK-2 and -4. The most common metastatic target proteins of -kauranes are MMP-2, MMP-9, VEGF, and VEGFR whereas LC-II and mTOR are key regulators to induce autophagy.

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