Fahimeh Alizadeh

Anti-cancer activity of secreted aspartyl proteinase protein from Candida tropicalis on human cervical cancer HeLa cells

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide. Microbial products are valuable sources of anti-cancer drugs. The aim of this study was to isolate secreted aspartyl proteinase protein from Candida tropicalis, investigate its inhibitory effect on human cervical cancer HeLa cells, and analyze the expression profiling of selected nuclear stem cell-associated transcription factors. The presence of secreted aspartyl proteinase protein was confirmed by the expression of SAP2 and SAP4 genes in C. tropicalis during the yeast-hyphae transition phase. The enzyme was purified and characterized using the aqueous two-phase system purification method, as well as proteolytic activity and the Bradford and micro-Kjeldahl methods, respectively. The in vitro anti-cancer properties of secreted aspartyl proteinase protein were evaluated by MTT assay, microscopic image analysis, nitric oxide (NO) scavenging activity assay, intracellular reactive oxygen species (ROS) production assay, and RT-qPCR. The isolated C. tropicalis secreted aspartyl proteinase protein exhibited proteinase activity with values ranging from 93.72 to 130.70 μg/mL and 89.88-127.72 μg/mL according to the Bradford and micro-Kjeldahl methods, respectively. Secreted aspartyl proteinase showed effective cytotoxicity in HeLa cell line leading to significant morphological changes. Additionally, it exhibited increased free radical scavenging activity compared to the untreated control group, as evidenced by nitrite inhibition. ROS production increased in HeLa cells exposed to secreted aspartyl proteinase. The expression levels of the nuclear stem cell-associated transcription factors octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homeobox (NANOG) were significantly downregulated in the HeLa cells treated with secreted aspartyl proteinase. Secreted aspartyl proteinase protein may be a promising anti-cancer agent, as it effectively affects gene expression and may ultimately reduce the development and progression of cervical cancer. Targeting the genes related to nuclear stem cell-associated transcription factors may provide a novel amenable to cancer treatment.

Association between dietary intake and risk of ovarian cancer: a systematic review and meta-analysis

It is unclear how dietary intake influences the ovarian cancer. The present paper sets out to systematically review and meta-analyze research on dietary intake to identify cases having high- or low-risk ovarian cancer. Scopus, PubMed, and Wiley Online Libraries were searched up to the date November 24, 2019. Two reviewers were requested to independently extract study characteristics and to assess the bias and applicability risks with reference to the study inclusion criteria. Meta-analyses were performed to specify the relationship between dietary intake and the risk of ovarian cancer identifying 97 cohort studies. No significant association was found between dietary intake and risk of ovarian cancer. The results of subgroup analyses indicated that green leafy vegetables (RR = 0.91, 95%, 0.85-0.98), allium vegetables (RR = 0.79, 95% CI 0.64-0.96), fiber (RR = 0.89, 95% CI 0.81-0.98), flavonoids (RR = 0.83, 95% CI 0.78-0.89) and green tea (RR = 0.61, 95% CI 0.49-0.76) intake could significantly reduce ovarian cancer risk. Total fat (RR = 1.10, 95% CI 1.02-1.18), saturated fat (RR = 1.11, 95% CI 1.01-1.22), saturated fatty acid (RR = 1.19, 95% CI 1.04-1.36), cholesterol (RR = 1.13, 95% CI 1.04-1.22) and retinol (RR = 1.14, 95% CI 1.00-1.30) intake could significantly increase ovarian cancer risk. In addition, acrylamide, nitrate, water disinfectants and polychlorinated biphenyls were significantly associated with an increased risk of ovarian cancer. These results could support recommendations to green leafy vegetables, allium vegetables, fiber, flavonoids and green tea intake for ovarian cancer prevention.