title: Co-treatment of Salinomycin Sensitizes AZD5363-treated Cancer Cells Through Increased Apoptosis.
abstract: AZD5363, an inhibitor of protein kinase B (AKT), is currently in clinical trials assessing the potential of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. The purpose of the present study was to identify conditions that increase the sensitivity of cancer cells to AZD5363. Microscopic examination revealed that treatment of cancer cells with a low concentration of salinomycin reduced cellular growth of AZD5363-treated breast cancer cells. Furthermore, fluorescence-activated cell sorting (FACS) analysis, Hoechst staining, and annexin V staining revealed that co-treatment with salinomycin sensitizes AZD5363-treated cancer cells via increased apoptosis with S-phase arrest. These results suggest that salinomycin can be applied to increase treatment efficacy for AZD5363-treated cancer cells. Our findings may contribute to improving the efficacy of the development of AZD5363-based sensitization therapies for patients with cancer.
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Ae-Ran
authors.initials: AR
authors.lastname: Choi
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Myung-Ji
authors.initials: MJ
authors.lastname: Jung
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Ju-Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea yoons@ncc.re.kr.
authors.forename: Sungpil
authors.initials: S
authors.lastname: Yoon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D011714:Pyrans / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D016196:S Phase; D000095662:Polyether Polyketides
chemical_list: D011714:Pyrans; D011743:Pyrimidines; D011758:Pyrroles; C010327:salinomycin; D000095662:Polyether Polyketides; C575618:capivasertib
keywords: AZD5363; apoptosis; cancer; salinomycin