title: Effects of G6PD activity inhibition on the viability, ROS generation and mechanical properties of cervical cancer cells.
abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been revealed to be involved in the efficacy to anti-cancer therapy but the mechanism remains unclear. We aimed to investigate the anti-cancer mechanism of G6PD deficiency. In our study, dehydroepiandrosterone (DHEA) and shRNA technology were used for inhibiting the activity of G6PD of cervical cancer cells. Peak Force QNM Atomic Force Microscopy was used to assess the changes of topography and biomechanical properties of cells and detect the effects on living cells in a natural aqueous environment. Flow cytometry was used to detect the apoptosis and reactive oxygen species (ROS) generation. Scanning electron microscopy was used to observe cell morphology. Moreover, a laser scanning confocal microscope was used to observe the alterations in cytoskeleton to explore the involved mechanism. When G6PD was inhibited by DHEA or RNA interference, the abnormal Young's modulus and increased roughness of cell membrane were observed in HeLa cells, as well as the idioblasts. Simultaneously, G6PD deficiency resulted in decreased HeLa cells migration and proliferation ability but increased ROS generation inducing apoptosis. What's more, the inhibition of G6PD activity caused the disorganization of microfilaments and microtubules of cytoskeletons and cell shrinkage. Our results indicated the anti-cervix cancer mechanism of G6PD deficiency may be involved with the decreased cancer cells migration and proliferation ability as a result of abnormal reorganization of cell cytoskeleton and abnormal biomechanical properties caused by the increased ROS. Suppression of G6PD may be a promising strategy in developing novel therapeutic methods for cervical cancer.
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Zishui
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Chengrui
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Rixin
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Luhao
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, University and Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education Guangzhou, 510080, China. Electronic address: jiangwy@mail.sysu.edu.cn.
authors.forename: Weiying
authors.initials: W
authors.lastname: Jiang
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001696:Biomechanical Phenomena / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D055119:Elastic Modulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology*
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D003687:Dehydroepiandrosterone; D005954:Glucosephosphate Dehydrogenase
keywords: Anti-tumor; Cervical cancer cell; Cytoskeleton; G6PD deficiency; Mechanical properties