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

  title={Mechanistic Pathways and Molecular Targets of Plant-Derived Anticancer ent-Kaurane Diterpenes},
  author={Md. Shahid Sarwar and Yi-Xuan Xia and Zheng-Ming Liang and Siu Wai Tsang and Hong-Jie Zhang},
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… Expand
Bioactive Ent-Kaurane Diterpenes Oridonin and Irudonin Prevent Cancer Cells Migration by Interacting with the Actin Cytoskeleton Controller Ezrin
The interesting activity profile, the good selectivity towards cancer cells, and the lower toxicity with respect to Oridonin, all suggest that Irudonin is a very promising anti-metastatic agent. Expand
Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I
To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). Expand
An ent‐Kaurane Diterpenoid Isolated from Rabdosia excisa Suppresses Bcr‐Abl Protein Expression in Vitro and in Vivo and Induces Apoptosis of CML Cells
It is found that kamebakaurin potently inhibits cell proliferation, mainly by enhancing cell apoptosis and down‐regulating Bcr‐Abl protein levels, and is a potential anticancer agent. Expand
NMR-Based Chemical Profiling, Isolation and Evaluation of the Cytotoxic Potential of the Diterpenoid Siderol from Cultivated Sideritis euboea Heldr.
The beneficial potential of siderol as a remarkable cytotoxic agent and the significant contribution of NMR spectroscopy towards the isolation and identification of this potent anticancer agent are unveiled. Expand
Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer
  • Ying Liu, Zan Song, +6 authors Hongmin Liu
  • Medicine
  • Acta pharmaceutica Sinica. B
  • 2021
The data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment. Expand
An Insight into the Anti-Angiogenic and Anti-Metastatic Effects of Oridonin: Current Knowledge and Future Potential
This review summarizes the recent applications of oridonin as an anti-angiogenic and anti-metastatic drug both in vitro and in vivo, and its potential mechanisms of action. Expand
Leukamenin E Induces K8/18 Phosphorylation and Blocks the Assembly of Keratin Filament Networks Through ERK Activation
It is proposed that leukamenin E-induced keratin phosphorylation may interfere with the initiation of KFs assembly and block the formation of a new KFs network, leading to the inhibition of cell spreading. Expand
Stevia Genus: Phytochemistry and Biological Activities Update
This review aims to present an update of the Stevia genus covering ethnobotanical aspects and traditional uses, phytochemistry, and biological activities of the extracts and isolated compounds. Expand
Nucleophosmin in Its Interaction with Ligands
The possible role of NPM1 inhibitors in the treatment of multiple cancers and other pathologies is emerging as a new therapeutic strategy. Expand
Phytochemical Omics in Medicinal Plants
  • J. Chen
  • Biology, Medicine
  • Biomolecules
  • 2020
This poster presents a probabilistic procedure to identify the phytochemical properties of the fruit extract of cannabis, which has shown promise in finding its application in medicine and cosmetics. Expand


Ponicidin, an Ent-Kaurane Diterpenoid Derived from a Constituent of the Herbal Supplement PC-SPES, Rabdosia rubescens, Induces Apoptosis by Activation of Caspase-3 and Mitochondrial Events in Lung Cancer Cells In Vitro
It is demonstrated that ponicidin exhibits cytotoxicity, induces apoptosis, disrupts the mitochondrial membrane potential, and triggers the activation of caspase-3, -8 and -9 in lung cancer A549 and GLC-82 cells, and it is concluded that ponicsidin has significant apoptosis-inducing effects. Expand
Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells.
The results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer. Expand
Pteisolic acid G, a novel ent-kaurane diterpenoid, inhibits viability and induces apoptosis in human colorectal carcinoma cells.
PAG, a novel inhibitor of the Wnt/β-catenin pathway and inducer of apoptosis, should be investigated in more detail using in vivo experiments and comprehensive mechanistic studies in order to examine the potential use of PAG as a novel therapeutic agent for the treatment of CRC. Expand
13-Hydroxy-15-oxo-zoapatlin, an ent-kaurane diterpene, induces apoptosis in human leukemia cells, affecting thiol-mediated redox regulation.
The proapoptotic activity of OZ was evaluated and it was found to induce hypodiploidia and phosphatidylserine externalization, two hallmarks of apoptosis; to disrupt mitochondrial membrane potential; and to trigger caspase-3 activation. Expand
Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis.
The results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis and induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Expand
Kaurene Diterpene Induces Apoptosis in Human Leukemia Cells Partly through a Caspase-8-Dependent Pathway
It is found that caspase-8, an apoptotic factor, is involved in KD-induced apoptosis, and KD may be a promising experimental cytotoxic agent that possibly points to new strategies to overcome a drug resistance. Expand
Anti-tumour activity of longikaurin A (LK-A), a novel natural diterpenoid, in nasopharyngeal carcinoma
The results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo. Expand
The natural diterpene ent-16β-17α-dihydroxykaurane down-regulates Bcl-2 by disruption of the Ap-2α/Rb transcription activating complex and induces E2F1 up-regulation in MCF-7 cells
This study confirms the regulation of Bcl-2 gene transcription by the Ap2α–Rb complex and describes a singular protein relocalization for Ap2 α induced by DHK, implicating a new potential therapeutic target to differentially onset apoptosis in tumor cells. Expand
Leukamenin E, an ent‐kaurane diterpenoid, is a novel and potential keratin intermediate filament inhibitor
It is proposed that leukamenin E is a novel inhibitor of KF assembly, and as such, can serve as a chemical probe of KFs functions and a potential molecular target for ent‐kaurane diterpenoid‐based therapeutics. Expand
The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells
It is demonstrated that oridonin interacts with Nucleolin, effectively modulating the activity of this multifunctional protein, which represents the first evidence of N nucleolin modulation by a small inhibitor. Expand