Journal
BIOMOLECULES
Volume 10, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/biom10010144
Keywords
isodon genus; ent-kaurane diterpenoids; cancer; natural compounds; pathways
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Funding
- Hong Kong PhD Fellowship Scheme (HKPFS)
- Research Grants Council of the Hong Kong Special Administrative Region, China [HKBU 12102219]
- Hong Kong Baptist University, Research Committee, Initiation Grant-Faculty Niche Research Areas [RC-IG-FNRA/17-18/12]
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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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