cyclin-d1 and naringenin

Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown.. This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms.. Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing.. Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus.. Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.

Topics: Animals; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin D1; DNA, Ribosomal; ErbB Receptors; Female; Flavanones; Gastrointestinal Microbiome; Gentian Violet; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases

In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G0/G1 and a G2/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively. Western blot analysis showed that MYR induced a decrease of Cyclin D1 in SCC-25 and of Cyclin B1 in HaCaT cells, while NAR negatively modulated Cyclin D1 expression in SCC-25 cells. Wound-healing and cell invasion assays demonstrated that both the flavonoids were able to reduce motility on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC because they exert cytostatic effect by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as antimetastatic agents. Therefore, MYR and NAR appear as promising candidate as oral cancer chemopreventive agents.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin B1; Cyclin D1; Flavanones; Flavonoids; Humans; Mouth Neoplasms; Signal Transduction; Wound Healing

Tumor cells are able to survive and proliferate in spite of their increased oxidative stress. This was taken as a hint for the implication of oxidants/antioxidants in the proliferation of glial-tumor cells. In the present study, an anti-proliferative effect of Naringenin, an antioxidant against cerebrally implanted C6 glioma cells in rats has been investigated. The status of lipid peroxidation/antioxidants, expressions of protein kinase C, nuclear factor κB, cyclin D1, cyclin dependent kinase 4, proliferating cell nuclear antigen, vascular endothelial growth factor, argyophillic nucleolar organizing regions and histopathology of brain tissues of control and experimental rats were analyzed. On supplementation of naringenin (50mg/kg BW for 30 days) to glioma induced rats, there was a reduction in lipid peroxidation with an increased antioxidant status. There was a significant decrease in the expressions of protein kinase C, nuclear factor κB, cyclin D1 and cyclin dependent kinase 4 on naringenin treatment. Further, the drug could modulate the glial-tumor cell proliferation as evidenced from the histopathological findings, argyophillic nucleolar organizing regions staining, proliferating cell nuclear antigen and vascular endothelial growth factor immunostaining. The findings suggest that naringenin could underlie the inhibition of glial tumor cell proliferation in C6 glioma models of rat.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain Neoplasms; Cell Growth Processes; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Flavanones; Glioma; Glutathione; Glutathione Peroxidase; Immunohistochemistry; Male; NF-kappa B; Proliferating Cell Nuclear Antigen; Protein Kinase C; Rats; Receptors, Peptide; Thiobarbituric Acid Reactive Substances; Vascular Endothelial Growth Factor A; Vitamin E

Estrogen receptor alpha (ERalpha) mediates 17beta-estradiol (E2) actions through the transcription of E2-sensitive target genes. In addition, rapid non-genomic signaling (e.g., MAPK/ERK) occurs. It is now well accepted that these rapid membrane-initiated responses account for E2-related cancer. Beside many beneficial effects on human health, nutritional flavonoids exert protective and anticarcinogenic effects on E2-related cancer. The mechanism underlying these effects seems to be related to flavonoids antioxidant properties and/or to their ability to alter signal transduction protein kinases. In addition, an antiestrogenic activity has been proposed but not yet defined. However, the identification and characterization of the responsible mechanisms for flavonoid antitumoral effects is poorly understood. Here, we investigated the possibility that the antimitogenic effects of flavonoids are transduced by modulating ERalpha-mediated rapid signaling. The ability of two flavonoids, the flavanone naringenin and the flavanol quercetin, with respect of E2, to induce ERalpha activities has been studied in the human cervix epitheloid carcinoma cell line (HeLa) devoid of any estrogen receptors and rendered E2-sensitive by transient transfection with a human ERalpha expression vector. Our results indicate that flavonoids act as E2 mimetic on ERalpha transcriptional activity, whereas they impair the activation of rapid signaling pathways committed to E2-induced proliferation. The resulting decoupling of ERalpha signal transduction could be proposed as a new mechanism in the protective effects of flavonoids against E2-related cancer.

Topics: Cyclin D1; Dose-Response Relationship, Drug; Estradiol; Estrogen Antagonists; Estrogen Receptor alpha; Flavanones; HeLa Cells; Humans; Neoplasms; Promoter Regions, Genetic; Quercetin; Time Factors