Inhibition of Cell Growth and VEGF Expression in Ovarian Cancer Cells by Flavonoids

Abstract

Dietary flavonoids have been shown to be protective against various types of cancers. Here we studied the effects of 12 different flavonoids and other substances on cell proliferation and VEGF expression in human ovarian cancer cells, OVCAR-3. Cell growth was determined to pinpoint the best time for drug treatment. By LDH assay, no cytotoxicity was observed for OVCAR-3 cells with all 12 chemicals except mevinolin. Six flavonoids, including apigenin, taxifolin, luteolin, quercetin, genistein, and kaempferol, were shown to inhibit the ovarian cancer cell growth in a dose-dependent manner. From both RT-qPCR and ELISA results, all flavonoids have shown varied degrees of inhibition in VEGF expression. Taxifolin and naringin showed the least inhibition effect. They both lack a double bond in the second ring structure that may be important in inhibiting VEGF expression. The rank order of VEGF protein secretion inhibitory potency was genistein > kaempferol > apigenin > quercetin > tocopherol > luteolin > cisplatin > rutin > naringin > taxifolin. Genistein, quercetin, and luteolin have shown strong inhibition to cell proliferation and VEGF expression of human ovarian cancer cells, and they show promising in the prevention of ovarian cancers.

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

“…In both platinum-sensitive and platinum-resistant ovarian cancer cells, genistein abrogated NF-jB DNA binding activity and down-regulated anti-apoptotic genes [59]. In addition, genistein suppressed VEGF expression in OVCAR-3 cells [37]. Among six flavonoids, genistein exhibited the most potent inhibitory effect on VEGF expression.…”

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

“…Cucurbitacin B (cucB), a triterpenoid from Cucurbitaceae vegetables also found in bitter melon seeds, caused cell cycle arrest and apoptosis induction in human colon adenocarcinoma cancer cells [53]. Additionally, Rutin, a flavonoid present in bitter melon leaves, has been reported to display growth inhibition of leukemia and ovarian carcinoma cells, with anti-invasive effects on melanoma cells [35,[56][57][58]. Therefore, BMLE may include other bioactive compounds apart from kuguacin J, which exert anti-tumor effects, although human studies have not yet been published.…”

“…Moreover, 2 flavonoids and 4 phenolic acids, including rutin, naringin, gentistic acid, benzoic acid, ocoumaric acid, and t-cinnamic acid, are present in bitter melon leaves [35]. Rutin, a flavonoid glycoside, has been reported to successfully show growth inhibition of leukemia and ovarian carcinomas, with anti-invasive effects on melanoma [35,[56][57][58]. Triterpenoids and flavoniods included in bitter melon leaf extract (BMLE) might be promising components with critical roles against cancer cell progression, but the active compound(s) remain to be identified.…”

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

“…15 Kaempferol is also effective in inhibiting angiogenesis and inducing apoptosis in ovarian cancer cells. [16][17][18][19] In human studies, a significant 40% decrease in incidence of ovarian cancer was found for individuals with the highest quintile of kaempferol intake as compared with those in the lowest quintile. 20 Despite promising preclinical results, the utility of such compounds for chemoprevention in humans has met with only limited success, largely due to inefficient systemic delivery and limited bioavailability of promising agents.…”

“…31 Chemoprevention of ovarian cancer using natural products has received more attention recently, and our earlier studies have indicated that kaempferol, a dietary flavonoid, is effective in inhibiting angiogenesis and inducing apoptosis in ovarian cancer cells. [16][17][18][19] However, effective concentrations are often above 20-40 µM, which are not always physiologically attainable. In this study, five nanoparticle formulations of kaempferol were developed and their efficacy in inhibiting the viability of malignant and normal ovarian cells was determined.…”