The tumor-growth inhibitory activity of flavanone and 2′-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs

Abstract

Natural products, including flavonoids, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, studies concerning the effect of flavonoids frequently lacked data regarding to flavanones. In this study, we investigated the inhibitory effect of flavanone compounds, including flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone, naringin and naringenin, on cell growth of various cancer cells. We determined that flavanone and 2'-OH flavanone inhibited cell growth of A549, LLC, AGS, SK-Hepl and HA22T cancer cells, while other flavanones showed little or no inhibition. We evaluated growth-inhibitory activity of flavanone and 2'-OH flavanone against highly proliferative human lung cancer cells (A549) via anchorage-independent and -dependent colony formation assay, and further showed that treatment of flavanone resulted in a G1 cell cycle arrest with reduction of cyclin D, E and cyclin-dependent kinase (CDK) 2, while treatment of 2'-OH flavanone led to a G2/M phase accumulation with reduction of cyclin B, D and Cdc2. Moreover, we demonstrated the improvement effect of flavanone and 2'-OH flavanone with anti-cancer drug, doxorubicin, on A549 cells. Finally, flavanone and 2'-OH flavanone were evidenced by its inhibition on the growth of A549 and Lewis lung carcinoma cells in vivo.

The Role of Phenolic Compounds in the Fight against Cancer – A Review

“…2'-OH Flavanone was once again the compound with the highest inhibition rates by triggering apoptosis and increasing p21. A very similar study was carried out by Hsiao et al [229] in 2007, where various flavanones were screened against human lung adenocarcinoma, Lewis lung adenocarcinoma, murine lung adenocarcinoma, human gastric epithelial adenocarcinoma and human hepatocellular …”

Combined treatment of 3-hydroxyflavone and imatinib mesylate increases apoptotic cell death of imatinib mesylate-resistant leukemia cells

“…Previous studies have shown that flavonoids with or without a single OH group had different effects on the viability of cancer cells [38]. Moreover, the presence of hydroxyl group in the structure of the flavonoids and the resonance of electrons between the A and B rings are very important for their biological activities [37,39,40]. According to previous studies and ours, we concluded that 3-HF might have a greater inhibitory effect on different cell lines compared to other dihydroxyflavones with a single OH group (Fig.…”

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

“…Moreover, naringin, a flavonone similar to hesperetin found in citrus species, when administered prior to DOX, acts as the dual modulator of P-gp expression, and it was hypothesized that this may be an attractive new agent for the chemosensitization of cancer cells [47]. Further, it has been reported that flavonone along with anticancer drug, DOX, showed inhibitory effect on the growth of A549 lung cancer cells as well as on Lewis lung carcinoma [48]. Hesperetin significantly induces G1-phase cell cycle arrest in human breast cancer MCF-7 cells through the regulation of CDK4 and p21 (Cip 1) pathways [49].…”