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Ref Type Journal Article
PMID (28011619)
Authors Sun X, Wang W, Chen J, Cai X, Yang J, Yang Y, Yan H, Cheng X, Ye J, Lu W, Hu C, Sun H, Pu J, Cao P
Title The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects.
Journal Vol Issue Date Pages Journal Short Title
Cancer research 77 4 2017 Feb 15 926-936 Cancer Res
URL
Abstract Text Aberrant expression of thioredoxin 1 (Trx1) plays an important role in cancer initiation and progression and has gained attention as an anticancer drug target. Here we report that the recently discovered natural diterpenoid isoforretin A (IsoA) significantly inhibits Trx1 activity and mediates anticancer effects in multiple preclinical settings. The inhibitory effect of IsoA was antagonized by free radical scavengers polyethylene glycol-catalase, polyethylene glycol superoxide dismutase, thiol-based antioxidants N-acetylcysteine and glutathione. Mass spectrometry analysis revealed that the mechanism of action was based on direct conjugation of IsoA to the Cys32/Cys35 residues of Trx1. This conjugation event attenuated reversible thiol reduction of Trx1, leading to ROS accumulation and a broader degradation of thiol redox homeostasis in cancer cells. Extending these in vitro findings, we documented that IsoA administration inhibited the growth of HepG2 tumors in a murine xenograft model of hepatocellular carcinoma. Taken together, our findings highlight IsoA as a potent bioactive inhibitor of Trx1 and a candidate anticancer natural product. Cancer Res; 77(4); 926-36. ©2016 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
IsoA IsoA 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
IsoA isoforretin A IsoA is a novel ent-kaurane diterpernoid derived from an Isodon plant, which may result in inhibition of cancer cell growth via suppression of Trx1, which leads to ROS build up (PMID: 28011619).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References