Journal of Biological Chemistry p. 22861 - 22867 (2016)
Update date:2022-08-10
Topics:
Zhang, Zhuzhen Z.
Lee, Eunice E.
Sudderth, Jessica
Yue, Yangbo
Zia, Ayesha
Glass, Donald
Deberardinis, Ralph J.
Wang, Richard C.
The discovery that oxidized vitamin C, dehydroascorbate (DHA), can induce oxidative stress and cell death in cancer cells has rekindled interest in the use of high dose vitamin C (VC) as a cancer therapy. However, high dose VC has shown limited efficacy in clinical trials, possibly due to the decreased bioavailability of oral VC. Because human erythrocytes express high levels of Glut1, take up DHA, and reduce it to VC, we tested how erythrocytes might impact high dose VC therapies. Cancer cells are protected from VC-mediated cell death when co-cultured with physiologically relevant numbers of erythrocytes. Pharmacological doses of VC induce oxidative stress, GSH depletion, and increased glucose flux through the oxidative pentose phosphate pathway (PPP) in erythrocytes. Incubation of erythrocytes with VC induced hemolysis, which was exacerbated in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD) patients and rescued by antioxidants. Thus, erythrocytes protect cancer cells from VC-induced oxidative stress and undergo hemolysis in vitro, despite activation of the PPP. These results have implications on the use of high dose VC in ongoing clinical trials and highlight the importance of the PPP in the response to oxidative stress.
View MoreSuzhou CarbonWell Pharma-Tech Co., Ltd
Contact:Tel: + 86 (0)512-8898-1216; + 86-18606258602
Address:2358 Changan Road, Wujiang Scientific Innovation Park, Wujiang, Jiangsu Province, P. R. China 215200
Tianjin Anda North Industrial & Business Co.Ltd.
Contact:86-22-24999306
Address:No.11 Erwei Road,Dongli Development Area,Tianjin,China
Contact:+44 (0)161 367 9441
Address:
QINGDAO ON-BILLION INDUSTRAIL CO.,LTD
website:http://www.obn.com.cn
Contact:+86-15005320811 +86-532-80681989
Address:F35 Parkson Mansion No.44-60 Zhongshan Rd.
Nanjing Samwon International Limited
Contact:+86-25-84873444
Address:1108, BLDG B, New Century Plaza, No 1, South Taiping Rd.,
Doi:10.1016/j.molstruc.2019.06.002
(2019)Doi:10.1016/j.tet.2006.03.058
(2006)Doi:10.1039/d0dt01090a
(2020)Doi:10.1002/jccs.201600286
(2016)Doi:10.1002/ejoc.202100580
(2021)Doi:10.1039/c7cc06077g
(2017)