Abstract
Ovarian cancer is one of the leading causes of female cancer death. Emerging evidence suggests that many dietary natural products have anti-tumorigenic activity, including that of asparagus officinalis. The current study aimed to assess the anti-tumorigenic and anti-metastatic effects of asparagus officinalis on serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer. Asparagus officinalis decreased cellular viability, caused cell cycle G1 phase arrest and induced apoptosis in the OVCAR5 and SKOV3 cells. Induction of apoptosis and inhibition of cell proliferation was rescued by the pan-caspase inhibitor, Z-VAD-FMK, implying that its cytotoxic effects were mainly dependent on caspase pathways. Asparagus officinalis increased levels of ROS and decreased mitochondrial membrane potential with corresponding increases in PERK, Bip, Calnexin PDI and ATF4 in both cell lines. Treatment with asparagus officinalis also reduced ability of adhesion and invasion through epithelial–mesenchymal transition and reduction of VEGF expression. The combination of Asparagus officinalis with paclitaxel had synergistic anti-proliferative activity. Furthermore, Asparagus officinalis significantly inhibited tumor growth and reduced serum VEGF in a genetically engineered mouse model of ovarian cancer under obese and lean conditions, accompanied with a decrease in the expression of Ki67, VEGF and phosphorylated S6, and in an increase in phosphorylation of AMPK in the ovarian tumor tissues. Overall, our data provide a pre-clinical rationale for asparagus officinalis in the prevention and treatment of ovarian cancer as a novel natural product.
Highlights
Ovarian cancer (OC) is the most lethal gynecologic malignancy and ranks fifth in overall cancer deaths in women, with an anticipated 21,410 new cases and 13,770 deaths anticipated for 2021 in the United States [1]
The OC cell lines OV433, OVCAR3, IGROV-1, Hey, OVCAR5 and SKOV3 were exposed for 72 hours to an extract of Asparagus officinalis (ASP) at concentrations varying from 0.01 to 15 mg/ml
Given that the colony formation assay is a well-established in vitro method for testing the proliferative capacity of treated cells, we evaluated the long-term effect of ASP on colony formation in the OC cell lines
Summary
Ovarian cancer (OC) is the most lethal gynecologic malignancy and ranks fifth in overall cancer deaths in women, with an anticipated 21,410 new cases and 13,770 deaths anticipated for 2021 in the United States [1]. Due to the lack of an effective method for the early detection of this disease and nonspecific symptoms at early stages, greater than 75% of ovarian cancer cases go undetected until an advanced stage, with an overall survival rate of less than 40% at 5 years [2, 3]. The mainstay of treatment for ovarian cancer is tumor debulking surgery followed by platinum and paclitaxel chemotherapy. Patients typically have high initial response rates, but the majority of patients are faced with a recurrence and platinum resistance despite significant advances in treatment strategies [3, 5]. Effective management of recurrence and chemo-resistance remains a significant challenge, and novel therapies including targeted therapy need to be developed to improve outcomes
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