Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors

• Published in: PloS one Vol. 8; no. 8; p. e72748
• Main Authors: De, Alok, De, Archana, Papasian, Chris, Hentges, Shane, Banerjee, Snigdha, Haque, Inamul, Banerjee, Sushanta K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-08-2013; Public Library of Science (PLoS)
• Subjects: Acids; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy - drug effects; Beclin-1; Blood vessels; Cancer; Cancer therapies; Cell death; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cellulose acetate; Chemokines; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Diet; Dietary supplements; Drug Synergism; Endothelial cells; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Glucose; Growth; Growth factors; Health aspects; Hematology; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factors; In vivo methods and tests; Laboratory animals; Medical prognosis; Medical research; Medicine; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Natural products; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - blood supply; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Phagocytosis; Phyllanthus emblica - chemistry; Plant extracts; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proteins; Quercetin; Radiation; Radiation therapy; Rodents; Surgery; Tumors; Xenograft Model Antitumor Assays; Xenografts; United States > US; Kansas City Missouri
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0072748

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.