title: Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway.
abstract: This study shows the effect of pterostilbene on intracellular neutral lipid accumulation in MCF-7 breast cancer cells leading to growth arrest and autophagy. On exposing the breast cancer cells with 30 μM pterostilbene for 72 h there was almost 2-folds increase in neutral lipids and triglycerides. Also the phytochemical caused a 4-folds increase in the expression of adipogenic differentiation marker c/EBPα. Further, pterostilbene inhibited 3β-hydroxylsterol-Δ(7)-reductase, the enzyme which catalyzes the last step conversion of 7-dehydrocholesterol to cholesterol, and thereby causes the intracellular accumulation of the former sterol. These results were associated with over-expression of oxysterol binding protein homologue and liver X receptor (LXR) by ~7-folds. Pterostilbene also caused a simultaneous increase in the expression autophagic marker proteins Beclin 1 and LC3 II (microtubule-associated protein 1 light chain 3) by approximately 6-folds, which leads to an alternative pathway of autophagy. These effects were observed in association with the loss of mitotic and metastatic potential of MCF-7 cells which was abolished in the presence of catalase (ROS scavenger) or 3MA (autophagic inhibitor). Thus the present data shows that the long term exposure to pterostilbene causes growth arrest in MCF-7 cells which may be due to differentiation of the mammary carcinoma cells into normal epithelial cell like morphology and activation of autophagy.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Ajanta
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Naganjaneyulu
authors.initials: N
authors.lastname: Bodipati
authors.forename: Marija Krstic
authors.initials: MK
authors.lastname: Demonacos
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Peddinti
authors.forename: Kaushik
authors.initials: K
authors.lastname: Ghosh
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000819:agonists / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003684:Dehydrocholesterols / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000071518:Liver X Receptors; D008565:Membrane Proteins / Q000819:agonists / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000819:agonists / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011987:Receptors, Steroid / Q000819:agonists / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis; D000098825:Oxysterol Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; D022762:CCAAT-Enhancer-Binding Proteins; D003684:Dehydrocholesterols; D000071518:Liver X Receptors; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D057093:Orphan Nuclear Receptors; D017382:Reactive Oxygen Species; D011987:Receptors, Steroid; D013267:Stilbenes; D014280:Triglycerides; D000098825:Oxysterol Binding Proteins; C107773:pterostilbene; C016705:7-dehydrocholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase