Inactivation of AKT, ERK and NF-κB by genistein derivative, 7-difluoromethoxyl-5,4′-di-n-octylygenistein, reduces ovarian carcinoma oncogenicity

Abstract

Abstract. Cancer stem cells (CSCs) have central functions in cancer formation and development. Aberrant expression of AKT, ERK and NF-κB signaling pathways have been reported in several types of CSCs. Phytochemicals from dietary compounds possess anti-CSC properties, and have been characterized as promising therapeutic agents for the prevention and treatment of many types of cancers. We previously showed that the newly synthesized genistein derivative, 7-difluoromethoxyl-5,4'-di-n-octylygenistein (DFOG), can inhibit the self-renewal ability of ovarian cancer stem cells (OVCSLCs). In the present study, we further assessed whether various signaling pathways are regulated by DFOG. We found that spheroids derived from the SKOV3 cell line possessed OVCSLC properties and DFOG efficiently inhibited the stemness of the OVCSLCs. In addition, the suppression of spheroid and colony formation by DFOG was associated with inhibition of AKT and ERK1/2 protein phosphorylation, and NF-κB activity in OVCSLCs from the SKOV3 cells. Importantly, DFOG inhibited the oncogenicity of the OVCSLCs by activation of FoxO3a and/or inactivation of FoxM1 by the targeting of multiple pro-survival (AKT and ERK1/2) and proinflammatory (NF-κB) pathways, providing a new avenue for the treatment of ovarian carcinoma in humans.

MicroRNA-320d regulates tumor growth and invasion by promoting FoxM1 and predicts poor outcome in gastric cardiac adenocarcinoma

“…The context scores of these sites are very high. Additionally, through the TCGA database, it revealed that FoxM1 is overexpressed in most cancer types, and the expression level is also associated with disease prognosis [17][18][19][20][21]. Therefore, in the present study, we associated FoxM1 with miR-320 in human GCA tissues, GCA cell lines and GCA-tumor-bearing mice, and found a negative correlation between miR-320d expression and FoxM1 expression, that is down-regulation of miR-320d could lead to increase FoxM1 expression both in mRNA level and protein level, which promote tumor progression and resulting in poor clinical prognosis.…”

“…After that, DAB (3.3′-diaminobenzidine tetrahydrochloride, BOSTER, China) was used as chromogen for positive FoxM1 visualization. The resulting slices were analyzed by two independent pathologists, and the IHC results were measured as previously described [17][18][19][20][21].…”

Fallopian tube precursor lesions of serous ovarian carcinoma require L1CAM for dissemination and metastasis

“…The upregulation of Integrin-ɑ5β1 has been shown to play an important role during tumorigenesis and in the promotion of metastasis in HGSC (Sawada et al 2008;Deng et al 2012;Kiefel et al 2012;Iwanicki et al 2016). Integrin-ɑ5β1 has also been implicated in sphere formation and activation of the AKT and ERK pathways (Casey and Skubitz 2000;Casey et al 2001;Ning et al 2017). The recruitment of Integrin-ɑ5β1 and fibronectin is important for the survival of cell aggregates that lose contact to their primary substratum, by helping to form anchorage to protect from anoikis (Yu et al 2012;Serres et al 2014).…”

Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study

“…Concerning the mechanisms of action linked with prognosis, let-7 has been involved in several signaling pathways, which could explain its prognostic implication. Suppression of oncogene HMGA2 [ 18 ], inhibition of stemness phenotype [ 19 , 20 ], reduction of phosphorylation of carcinogenic signaling as AKT [ 21 ], influence in immunomodulation [ 22 ], suppression of proliferation [ 23 , 24 ] and control of invasion/migration [ 25 , 26 ] are among the different mechanisms by which let-7 can modulate tumor prognosis.…”