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

1
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
2
Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 144; https://doi.org/10.3390/biom10010144
Received: 18 December 2019 / Revised: 12 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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. View Full-Text
Keywords: isodon genus; ent-kaurane diterpenoids; cancer; natural compounds; pathways isodon genus; ent-kaurane diterpenoids; cancer; natural compounds; pathways
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MDPI and ACS Style

Sarwar, M.S.; Xia, Y.-X.; Liang, Z.-M.; Tsang, S.W.; Zhang, H.-J. Mechanistic Pathways and Molecular Targets of Plant-Derived Anticancer ent-Kaurane Diterpenes. Biomolecules 2020, 10, 144.

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