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 Emblica officinalis (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.

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

“…In this study, we observed a role for HIF-1a in BAG3-regulated VEGF and MMP2 expression which was consistent with previous reports that HIF-1a promotes VEGF and MMP2 expression, enhancing angiogenesis and metastasis of HCC. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Moreover, BAG3 regulated angiogenesis of HCC cells through ERK phosphorylation, in accordance with previous studies. 12 Earlier work showed that autophagy-related genes could downregulate angiogenesis; 18,19 however, in our study, knockdown of BAG3 could downregulate the autophagy process.…”

“…Recent reports point to a role for BAG3 in controlling autophagy-related genes which could, in turn, regulate angiogenensis. 18,19 We analyzed autophagy markers (LC3A/B and Atg5) by western blotting. We found that Atg5 was significantly decreased after BAG3 knockdown, and that LC3A/B was decreased in the MHCC-LM3 cell line ( Figure 7).…”

Basic Studies on Chemopreventive Properties of Quercetin and Curcumin and Other Plant-origin Compounds in Ovarian Cancer Cells – A Mini-review

“…with 80 mg/kg of quercetin twice a week; 30 mg/kg 3MA twice a week; a combination of 30 mg/kg 3 MA and 80 mg/kg of quercetin twice a week; or a vehicle control injected with the same volume of saline for 4 weeks [78]. The results of this study are consistent with the trend of predecessor studies [56,60,77] showing that quercetin has the potential to induce protective autophagy in cancer cells through AKT-mTOR and hypoxia-induced factor 1α signaling [79,80] and in this way to induce autophagy in ovarian cancer cells [81].…”

The critical role of HMGA2 in regulation of EMT in epithelial ovarian carcinomas

“…HMGA2 is reported to promote proliferation and migration/ invasion of cancer cells, including breast and liver cancer cells [16][17][18], while the significance and role of HMGA2 in EOC is still unknown. Our present work suggests the critical role of HMGA2 in EOC development via in vitro assays.…”