title: Statil suppresses cancer cell growth and proliferation by the inhibition of tumor marker AKR1B10.
abstract: Aldo-keto reductase 1B10 (AKR1B10) is an oncogenic carbonyl reductase that eliminates α,β-unsaturated carbonyl compounds/lipid peroxides and mediates retinoic acid signaling. Targeted inhibition of AKR1B10 activity is a newly emerging strategy for cancer therapy. This study evaluated the inhibitory activity of a small chemical statil towards AKR1B10 and tested its antiproliferative activity in breast (BT-20) and lung (NCI-H460) cancer cells that express AKR1B10. Experimental results showed that statil inhibited AKR1B10 enzyme activity efficiently, with an IC50 at 0.21±0.06 µmol/l. Exposing BT-20 and NCI-H460 cells to statil and diclofenac, a selective AKR1B10 inhibitor, led to dose-dependent inhibition of cell growth and proliferation and plating efficiency. At higher doses (50 µmol/l or higher), statil induced cell death with apoptotic characteristics, such as DNA fragmentation and Annexin-V staining. Furthermore, statil enhanced the susceptibility of cells to acrolein, an active substrate of AKR1B10. Taken together, these data suggest that statil possesses potent antiproliferative activity by inhibiting AKR1B10 activity.
authors.affiliation: aGuangdong Key Laboratory for Diagnosis & Treatment of Emerging Infectious Diseases bShenzhen Key Laboratory of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen cState Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Hunan, China dDepartment of Medical Microbiology, Immunology, & Cell Biology, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cao
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004249:DNA Damage; D004008:Diclofenac / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms; D010793:Phthalazines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010793:Phthalazines; D004008:Diclofenac; C042829:ponalrestat; D000171:Acrolein; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase