Abstract
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.
Keywords:
LY303511; oral cancer; oxidative stress; preferential killing; zebrafish xenograft model.
© 2019 Wiley Periodicals, Inc.
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use*
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Apoptosis
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chromones / therapeutic use*
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DNA Damage
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Humans
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Mouth Neoplasms / drug therapy*
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Mouth Neoplasms / metabolism
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Mouth Neoplasms / pathology
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Oxidative Stress
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Piperazines / therapeutic use*
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Reactive Oxygen Species / metabolism
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Zebrafish
Substances
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Antineoplastic Agents
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Chromones
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Piperazines
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Reactive Oxygen Species
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LY 303511
Grants and funding
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MOHW108-TDU-B-212-124016/Health and Welfare Surcharge of Tobacco Products, the Ministry of Health and Welfare, Taiwan, Republic of China
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KMUH105-5M24/Kaohsiung Medical University Hospital
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KMUH107-7R74/Kaohsiung Medical University Hospital
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MOST 107-2314-B-037-048/Ministry of Science and Technology, Taiwan
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MOST 107-2314-B-037-057/Ministry of Science and Technology, Taiwan
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MOST 107-2320-B-037-016/Ministry of Science and Technology, Taiwan
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MOST 107-2628-B-037-001/Ministry of Science and Technology, Taiwan
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MOST107-2311-B-037-001/Ministry of Science and Technology, Taiwan
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#NSYSUKMU 108-P001/National Sun Yat-sen University-KMU Joint Research Project
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NSYSUKMU 108-P001/National Sun Yat-sen University-KMU Joint Research Project
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Ministry of Health and Welfare, Taiwan, Republic of China
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Health and Welfare Surcharge of Tobacco Products
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108-CCH-KMU-008/ChangHua Christian Hospital-KMU Fund
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Kaohsiung Medical University
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Ministry of Science and Technology