PMID- 31115172 OWN - NLM STAT- MEDLINE DCOM- 20190903 LR - 20190903 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 34 IP - 8 DP - 2019 Aug TI - LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo. PG - 958-967 LID - 10.1002/tox.22767 [doi] AB - LY303511 was developed as a negative control of LY294002 without pan-phosphoinositide 3-kinase (PI3K) inhibition. We hypothesize LY303511 generate reactive oxygen species (ROS) to induce apoptosis for killing oral cancer cells. In MTS assay, LY303511 dose-responsively decreases survival in three kinds of oral cancer cells but little damage to normal oral cells (HGF-1). Two oral cancer cells (CAL 27 and SCC-9) with highly sensitivity to LY303511 were used. In 7-aminoactinomycin D (7AAD) assay, LY303511 slightly increases subG1 population in oral cancer cells. In annexin V/7AAD and/or pancaspase assays, LY303511 induces apoptosis in oral cancer cells but HGF-1 cells remains in basal level. In oxidative stress, LY303511 induces ROS and mitochondrial superoxide in oral cancer cells. In 8-oxo-2'-deoxyguanosine assay, LY303511 induces oxidative DNA damage in oral cancer cells. In zebrafish model, LY303511 inhibits CAL 27-xenografted tumor growth. Therefore, LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Tang, Jen-Yang AU - Tang JY AD - Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Xu, Yi-Hua AU - Xu YH AD - Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Lin, Li-Ching AU - Lin LC AD - Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan, Taiwan. AD - School of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Chung Hwa University of Medical Technology, Tainan, Taiwan. FAU - Ou-Yang, Fu AU - Ou-Yang F AD - Division of Breast Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Wu, Kuang-Han AU - Wu KH AD - Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Tsao, Li-Yi AU - Tsao LY AD - Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Yu, Tzu-Jung AU - Yu TJ AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Huang, Hurng-Wern AU - Huang HW AD - Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Wang, Hui-Ru AU - Wang HR AD - Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Liu, Wangta AU - Liu W AD - Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chang, Hsueh-Wei AU - Chang HW AUID- ORCID: 0000-0003-0068-2366 AD - Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. LA - eng GR - MOHW108-TDU-B-212-124016/Health and Welfare Surcharge of Tobacco Products, the Ministry of Health and Welfare, Taiwan, Republic of China/ GR - KMUH105-5M24/Kaohsiung Medical University Hospital/ GR - KMUH107-7R74/Kaohsiung Medical University Hospital/ GR - MOST 107-2314-B-037-048/Ministry of Science and Technology, Taiwan/ GR - MOST 107-2314-B-037-057/Ministry of Science and Technology, Taiwan/ GR - MOST 107-2320-B-037-016/Ministry of Science and Technology, Taiwan/ GR - MOST 107-2628-B-037-001/Ministry of Science and Technology, Taiwan/ GR - MOST107-2311-B-037-001/Ministry of Science and Technology, Taiwan/ GR - #NSYSUKMU 108-P001/National Sun Yat-sen University-KMU Joint Research Project/ GR - NSYSUKMU 108-P001/National Sun Yat-sen University-KMU Joint Research Project/ GR - Ministry of Health and Welfare, Taiwan, Republic of China/ GR - Health and Welfare Surcharge of Tobacco Products/ GR - 108-CCH-KMU-008/ChangHua Christian Hospital-KMU Fund/ GR - Kaohsiung Medical University/ GR - Ministry of Science and Technology/ PT - Journal Article DEP - 20190521 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 0 (Antineoplastic Agents) RN - 0 (Chromones) RN - 0 (Piperazines) RN - 0 (Reactive Oxygen Species) RN - 154447-38-8 (LY 303511) SB - IM MH - Animals MH - Antineoplastic Agents/*therapeutic use MH - Apoptosis MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Chromones/*therapeutic use MH - DNA Damage MH - Humans MH - Mouth Neoplasms/*drug therapy/metabolism/pathology MH - Oxidative Stress MH - Piperazines/*therapeutic use MH - Reactive Oxygen Species/metabolism MH - Zebrafish OTO - NOTNLM OT - LY303511 OT - oral cancer OT - oxidative stress OT - preferential killing OT - zebrafish xenograft model EDAT- 2019/05/23 06:00 MHDA- 2019/09/04 06:00 CRDT- 2019/05/23 06:00 PHST- 2019/02/14 00:00 [received] PHST- 2019/04/17 00:00 [revised] PHST- 2019/04/24 00:00 [accepted] PHST- 2019/05/23 06:00 [pubmed] PHST- 2019/09/04 06:00 [medline] PHST- 2019/05/23 06:00 [entrez] AID - 10.1002/tox.22767 [doi] PST - ppublish SO - Environ Toxicol. 2019 Aug;34(8):958-967. doi: 10.1002/tox.22767. Epub 2019 May 21.