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

Authors
  • sarwar, md. shahid
  • xia, yi-xuan
  • liang, zheng-ming
  • tsang, siu wai
  • zhang, hong-jie
Publication Date
Jan 16, 2020
Source
MDPI
Keywords
Language
English
License
Green
External links

Abstract

Since the first discovery in 1961, more than 1300 ent-kaurane diterpenoids have been isolated and identified from different plant sources, mainly the genus Isodon. 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 ent-kaurane compounds in a series of cancer cell lines. Oridonin is one of the prime anticancer ent-kaurane diterpenoids that is currently in a phase-I clinical trial in China. In this review, we have extensively summarized the anticancer activities of ent-kaurane diterpenoids according to their plant sources, mechanistic pathways, and biological targets. Literature analysis found that anticancer effect of ent-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 ent-kauranes are MMP-2, MMP-9, VEGF, and VEGFR whereas LC-II and mTOR are key regulators to induce autophagy.

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