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Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer.
Apoptosis. 2016 11; 21(11):1265-1278.A

Abstract

A principal limitation to the clinical use of cisplatin is the high incidence of chemoresistance to this drug. Combination treatments with other drugs may help to circumvent this problem. Wogonin, one of the major natural flavonoids, is known to reverse multidrug resistance in several types of cancers. We investigated the ability of wogonin to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R) and their parental and other human HNC cell lines were used. The effects of wogonin, either alone or in combination with cisplatin, were assessed in HNC cells and normal cells using cell cycle and death assays and by measuring cell viability, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models. Wogonin selectively killed HNC cells but spared normal cells. It inhibited nuclear factor erythroid 2-related factor 2 and glutathione S-transferase P in cisplatin-resistant HNC cells, resulting in increased ROS accumulation in HNC cells, an effect that could be blocked by the antioxidant N-acetyl-L-cysteine. Wogonin also induced selective cell death by targeting the antioxidant defense mechanisms enhanced in the resistant HNC cells and activating cell death pathways involving PUMA and PARP. Hence, wogonin significantly sensitized resistant HNC cells to cisplatin both in vitro and in vivo. Wogonin is a promising anticancer candidate that induces ROS accumulation and selective cytotoxicity in HNC cells and can help to overcome cisplatin-resistance in this cancer.

Authors+Show Affiliations

Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. rohjl@amc.seoul.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27544755

Citation

Kim, Eun Hye, et al. "Targeting Nrf2 With Wogonin Overcomes Cisplatin Resistance in Head and Neck Cancer." Apoptosis : an International Journal On Programmed Cell Death, vol. 21, no. 11, 2016, pp. 1265-1278.
Kim EH, Jang H, Shin D, et al. Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. Apoptosis. 2016;21(11):1265-1278.
Kim, E. H., Jang, H., Shin, D., Baek, S. H., & Roh, J. L. (2016). Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. Apoptosis : an International Journal On Programmed Cell Death, 21(11), 1265-1278.
Kim EH, et al. Targeting Nrf2 With Wogonin Overcomes Cisplatin Resistance in Head and Neck Cancer. Apoptosis. 2016;21(11):1265-1278. PubMed PMID: 27544755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. AU - Kim,Eun Hye, AU - Jang,Hyejin, AU - Shin,Daiha, AU - Baek,Seung Ho, AU - Roh,Jong-Lyel, PY - 2016/8/22/pubmed PY - 2018/2/13/medline PY - 2016/8/22/entrez KW - Cell death KW - Cisplatin resistance KW - Head and neck cancer KW - Reactive oxygen species KW - Wogonin SP - 1265 EP - 1278 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 21 IS - 11 N2 - A principal limitation to the clinical use of cisplatin is the high incidence of chemoresistance to this drug. Combination treatments with other drugs may help to circumvent this problem. Wogonin, one of the major natural flavonoids, is known to reverse multidrug resistance in several types of cancers. We investigated the ability of wogonin to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R) and their parental and other human HNC cell lines were used. The effects of wogonin, either alone or in combination with cisplatin, were assessed in HNC cells and normal cells using cell cycle and death assays and by measuring cell viability, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models. Wogonin selectively killed HNC cells but spared normal cells. It inhibited nuclear factor erythroid 2-related factor 2 and glutathione S-transferase P in cisplatin-resistant HNC cells, resulting in increased ROS accumulation in HNC cells, an effect that could be blocked by the antioxidant N-acetyl-L-cysteine. Wogonin also induced selective cell death by targeting the antioxidant defense mechanisms enhanced in the resistant HNC cells and activating cell death pathways involving PUMA and PARP. Hence, wogonin significantly sensitized resistant HNC cells to cisplatin both in vitro and in vivo. Wogonin is a promising anticancer candidate that induces ROS accumulation and selective cytotoxicity in HNC cells and can help to overcome cisplatin-resistance in this cancer. SN - 1573-675X UR - https://www.unboundmedicine.com/medline/citation/27544755/Targeting_Nrf2_with_wogonin_overcomes_cisplatin_resistance_in_head_and_neck_cancer_ L2 - https://doi.org/10.1007/s10495-016-1284-8 DB - PRIME DP - Unbound Medicine ER -