Department of OB/GYN, School of Medicine, University of Missouri Kansas City, Kansas City, Missouri, United States of America.
PLoS One. 2013 Aug 15;8(8):e72748. doi: 10.1371/journal.pone.0072748. eCollection 2013.
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.
患有卵巢癌(OC)的患者可能会接受手术、化疗和/或放射治疗,但这些策略都不是非常有效。一些植物源性天然产物/膳食补充剂,包括余甘子(Amla)提取物,已显示出强大的抗肿瘤特性。在这项研究中,我们确定 Amla 提取物(AE)在体外和体内条件下对 OC 细胞具有抗增殖作用。我们还确定了 AE 的一种成分槲皮素在体外条件下对 OC 细胞的抗增殖作用。AE 不会诱导细胞凋亡,但在体外条件下显著增加自噬蛋白 beclin1 和 LC3B-II 的表达。槲皮素也增加了自噬蛋白 beclin1 和 LC3B-II 的表达在体外条件下。AE 还显著降低了几种血管生成基因的表达,包括 OVCAR3 细胞中的缺氧诱导因子 1α(HIF-1α)。AE 与顺铂协同作用,减少细胞增殖并增加自噬蛋白 beclin1 和 LC3B-II 的表达在体外条件下。AE 还对小鼠异种移植肿瘤具有抗增殖作用,并诱导自噬蛋白 beclin1 和 LC3B-II 的表达。此外,AE 减少了小鼠异种移植肿瘤中内皮细胞抗原-CD31 阳性血管和 HIF-1α 的表达。总之,这些研究表明,AE 可能通过抑制血管生成和激活 OC 中的自噬来抑制 OC 细胞的体外和体内生长。因此,AE 可能作为一种替代或辅助治疗方法,有助于对抗 OC。