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.
Highlights
Cancer is a heterogeneous disease which caused 9.6 million deaths globally in 2018 and the incidence of cancer is projected to increase to 13.1 million deaths by 2030 [1,2]
Oridonin potentiated the anticancer activity of lentinan, a polysaccharide isolated from shiitake mushrooms, by upregulating the expression levels of caspase-3, -8, -9, BAX, p53, and p21 while downregulating the expression of B-cell lymphoma 2 (BCL-2), B-cell lymphoma extra-large (BCL-XL ) and epidermal growth factor (EGF) in SMMC-7721 human hepatoma cells [29]
Nature has blessed humanity with a wide variety of drugs for the treatment of cancer, and over the Nature last fewhas decades large number natural products have widely investigated forover their blesseda humanity with of a wide variety of drugs forbeen the treatment of cancer, and anticancer recent years, ent-kaurane diterpenoids attentionfor from the the last fewpotential
Summary
Cancer is a heterogeneous disease which caused 9.6 million deaths globally in 2018 and the incidence of cancer is projected to increase to 13.1 million deaths by 2030 [1,2]. Used anticancer drugs are mainly obtained from natural sources (plants, microorganisms, and marine organisms) or from synthetic reactions [3]. Most of these drugs kill normal cells generating severe side effects [4,5]. With the exception of those compounds containing an alkene nomenclature, and numbering of the ent-kaurane skeleton. For theThis specific rotation [12] This class of compounds mainly available in consists of a group of flowering plants. We discuss the anticancer ent-kaurane diterpenoids reported in the literature regulated thissource type ofand compound.
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