Apigenin inhibits renal cell carcinoma cell proliferation

Abstract

Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

Cytochrome P450 CYP1 metabolism of hydroxylated flavones and flavonols: Selective bioactivation of luteolin in breast cancer cells

“…With regard to their biological activity, several reports have suggested antioxidant, antimutagenic and antiproliferative modes of action (de Oliveira et al, 2013;Peng et al, 2003;Gordo et al, 2012;Nagao et al, 2002). It is important to note that luteolin was more potent than apigenin in HeLa cervical carcinoma and B16F10 melanoma cells, whereas 6 OH luteolin was more Zhang et al, 2009;Meng et al, 2017;Chen et al, 2017;Sonoki et al, 2017).…”

Flavonoids as Anticancer Agents

“…In PC-3 and DU145 cell lines apigenin induced Bax overexpression, the downregulation of Bcl-2 and Bcl-xL proteins, and stimulated cytochrome c release from mitochondria and subsequent activation of signaling cascades [124,125]. Apigenin upregulated p53 in ACHN, Caki-1 RCC cell lines [126]. In T24 cell line, apigenin inactivated PI3K/Akt signaling pathway, activated the intrinsic apoptotic pathway, promoted the cytochrome c release from mitochondria, inhibited Bcl-xL [127,128].…”

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

“…Another class of promising M pro inhibitors has been identified in flavonoids such as Apigenin-7-O-neohesperidoside, Luteolin-7-rutinoside, and Resinoside. These compounds are also widespread on terrestrial plants and in food waste with good anti-tumor, anti-inflammatory, and antioxidant activity [31][32][33][34][35]. Among these, Apigenin-7-O-neohesperidoside or Rhoifolin (whose structure belongs to flavone glycoside and its aglycone is apigenin, while the neohesperidose disaccharide constitutes the glycosidic structure) has the best binding energy (−12.39 kcal/mol).…”