American Association for Cancer Research
15357163mct160332-sup-166850_1_supp_data_3602747_7b175g.png (763.33 kB)

Supplementary Figure S3 from A Novel Polyphenol Conjugate Sensitizes Cisplatin-Resistant Head and Neck Cancer Cells to Cisplatin via Nrf2 Inhibition

Download (763.33 kB)
posted on 2023-04-03, 15:25 authored by Eun Hye Kim, Hyejin Jang, Jong-Lyel Roh

Supplementary Figure S3. The effects of DPP-23 on Nrf2, p53 and its target proteins, cleaved PARP, and p21WAF1 in HN9-cisR cells with wild-type p53 and p53 knock down. Western blotting was performed in the cells that were transfected with scrambled siRNA (scr) or p53 siRNA for 48 h and then, exposed to different concentrations of DPP-23 for 24 h.



Ministry of Science, ICT and Future Planning


Ministry of Health and Welfare

Republic of Korea



Many cancer cells show acquired resistance to chemotherapeutic agents, such as cisplatin. This is a major cause of cancer treatment failure, and novel agents to overcome resistance are thus urgently required. A novel synthetic polyphenol conjugate, (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP-23), selectively kills tumor cells via the reactive oxygen species (ROS)–mediated unfolded protein response. We investigated the ability of DPP-23 to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Cisplatin-resistant HNC cell lines and their parental and other HNC cell lines were used. The effects of cisplatin and DPP-23 were assessed alone and in combination in HNC and normal cells using cell viability, cell cycle, and cell death assays, by measuring glutathione (GSH), ROS, and protein levels, and via preclinical mouse studies. DPP-23 induced selective cell death in HNC cells, including cisplatin-resistant HNC cells, but spared normal cells, via cellular GSH depletion and ROS accumulation. The effect was blocked by the antioxidant N-acetyl-L-cysteine. DPP-23 activated p53 and its related cell death pathways via a robust accumulation of cellular ROS that involved inhibition of nuclear factor erythroid 2–related factor 2 antioxidant defense mechanisms. Thus, DPP-23 significantly overcame cisplatin resistance in HNC cells in vitro and in vivo. As a promising anticancer strategy, ROS generation and subsequent selective cancer cell killing by DPP-23 might help to overcome cisplatin resistance in HNC. Mol Cancer Ther; 15(11); 2620–9. ©2016 AACR.

Usage metrics

    Molecular Cancer Therapeutics



    Ref. manager