title: Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors.
abstract: Patients with ovarian cancer (OC) may be treated with surgery, chemotherapy and/or radiation therapy, although none of these strategies are very effective. Several plant-based natural products/dietary supplements, including extracts from Emblicaofficinalis (Amla), have demonstrated potent anti-neoplastic properties. In this study we determined that Amla extract (AE) has anti-proliferative effects on OC cells under both in vitro and in vivo conditions. We also determined the anti-proliferative effects one of the components of AE, quercetin, on OC cells under in vitro conditions. AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. Quercetin also increased the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1α (HIF-1α) in OVCAR3 cells. AE acted synergistically with cisplatin to reduce cell proliferation and increase expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also had anti-proliferative effects and induced the expression of the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors. Additionally, AE reduced endothelial cell antigen - CD31 positive blood vessels and HIF-1α expression in mouse xenograft tumors. Together, these studies indicate that AE inhibits OC cell growth both in vitro and in vivo possibly via inhibition of angiogenesis and activation of autophagy in OC. Thus AE may prove useful as an alternative or adjunct therapeutic approach in helping to fight OC.
authors.affiliation: Department of OB/GYN, School of Medicine, University of Missouri Kansas City, Kansas City, Missouri, United States of America.
authors.forename: Alok
authors.initials: A
authors.lastname: De
authors.forename: Archana
authors.initials: A
authors.lastname: De
authors.forename: Chris
authors.initials: C
authors.lastname: Papasian
authors.forename: Shane
authors.initials: S
authors.lastname: Hentges
authors.forename: Snigdha
authors.initials: S
authors.lastname: Banerjee
authors.forename: Inamul
authors.initials: I
authors.lastname: Haque
authors.forename: Sushanta K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D029842:Phyllanthus emblica / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D002945:Cisplatin