Anticancer activity of 2'-hydroxyflavanone towards lung cancer.

Anticancer activity of 2'-hydroxyflavanone towards lung cancer. Oncotarget. 2018 Nov 16;9(90):36202-36219 Authors: Awasthi S, Singhal SS, Singhal J, Nagaprashantha L, Li H, Yuan YC, Liu Z, Berz D, Igid H, Green WC, Tijani L, Tonk V, Rajan A, Awasthi Y, Singh SP Abstract In previous studies, we found that 2'-hydroxyflavonone (2HF), a citrus flavonoid, inhibits the growth of renal cell carcinoma in a VHL-dependent manner. This was associated with the inhibition of glutathione S-transferases (GSTs), the first step enzyme of the mercapturic acid pathway that catalyzes formation of glutathione-electrophile conjugates (GS-E). We studied 2HF in small cell (SCLC) and non-small cell (NSCLC) lung cancer cell lines for sensitivity to 2HF antineoplastic activity and to determine the role of the GS-E transporter Rlip (Ral-interacting protein; RLIP76; RALBP1) in the mechanism of action of 2HF. Our results show that 2HF induced apoptosis in both histological types of lung cancer and inhibited proliferation and growth through suppression of CDK4, CCNB1, PIK3CA, AKT and RPS6KB1 (P70S6K) signaling. Increased E-cadherin and reduced fibronectin and vimentin indicated inhibition of epithelial-mesenchymal transition. Additionally, 2HF inhibited efflux of doxorubicin and increased its accumulation in the cells, but did not add to the transport inhibitory effect of anti-Rlip antibodies alone. Binding of Rlip to 2HF was evident from successful purification o...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research