Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6K and ERK signaling pathways.

Abstract	Mollugin, a bioactive phytochemical isolated from Rubia cordifolia L., has shown preclinical anticancer efficacy in various cancer models. However the effects of mollugin in regulating cancer cell survival and death remains undefined. In the present study we found that mollugin exhibited cytotoxicity on various cancer models. The suppression of cell viability was due to the induction of mitochondria apoptosis. In addition, the presence of autophagic hallmarks was observed in mollugin-treated cells. Notably, blockade of autophagy by a chemical inhibitor or RNA interference enhanced the cytotoxicity of mollugin. Further experiments demonstrated that phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) and extracellular regulated protein kinases (ERK) signaling pathways participated in mollugin-induced autophagy and apoptosis. Together, these findings support further studies of mollugin as candidate for treatment of human cancer cells.
Authors	Li Zhang, Handong Wang, Jianhong Zhu, Jianguo Xu, Ke Ding
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 450 Issue 1 Pg. 247-54 (Jul 18 2014) ISSN: 1090-2104 [Electronic] United States
PMID	24887566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2014 Elsevier Inc. All rights reserved.
Chemical References	Drugs, Chinese Herbal Pyrans rubimaillin MTOR protein, human Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases, 70-kDa TOR Serine-Threonine Kinases
Topics	Animals Cell Death (drug effects) Cell Line, Tumor Dose-Response Relationship, Drug Drugs, Chinese Herbal (administration & dosage) Humans MAP Kinase Signaling System (drug effects) Mice Neoplasms, Experimental (metabolism, pathology) Phosphatidylinositol 3-Kinases (metabolism) Proto-Oncogene Proteins c-akt (metabolism) Pyrans (administration & dosage) Ribosomal Protein S6 Kinases, 70-kDa (metabolism) TOR Serine-Threonine Kinases (metabolism)

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