LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo

• Published in: Environmental toxicology Vol. 34; no. 8; pp. 958 - 967
• Main Authors: Tang, Jen‐Yang, Xu, Yi‐Hua, Lin, Li‐Ching, Ou‐Yang, Fu, Wu, Kuang‐Han, Tsao, Li‐Yi, Yu, Tzu‐Jung, Huang, Hurng‐Wern, Wang, Hui‐Ru, Liu, Wangta, Chang, Hsueh‐Wei
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2019; Wiley Subscription Services, Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; 8-Hydroxydeoxyguanosine; Annexin V; Apoptosis; Assaying; Cancer; Cells; Danio rerio; Displays; DNA; DNA damage; Freshwater fishes; Health risk assessment; Kinases; LY303511; Mitochondria; mouth neoplasms; neoplasm cells; Neoplasms; Oral cancer; Oxidative stress; phosphatidylinositol 3-kinase; preferential killing; Reactive oxygen species; Superoxide; Survival; Xenografts; Zebrafish; zebrafish xenograft model; LY303511; preferential killing; oral cancer; oxidative stress; zebrafish xenograft model
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.22767

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.