PMID- 32756347 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 9 IP - 8 DP - 2020 Aug 3 TI - Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress. LID - 10.3390/antiox9080694 [doi] LID - 694 AB - Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of gammaH2AX and 8-oxo-2'deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage. FAU - Tang, Jen-Yang AU - Tang JY AUID- ORCID: 0000-0002-5690-0708 AD - Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. FAU - Wu, Kuang-Han AU - Wu KH AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Wang, Yen-Yun AU - Wang YY AD - School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. AD - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Farooqi, Ammad Ahmad AU - Farooqi AA AD - Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan. FAU - Huang, Hurng-Wern AU - Huang HW AD - Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. FAU - Yuan, Shyng-Shiou F AU - Yuan SF AUID- ORCID: 0000-0002-4753-788X AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. AD - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. FAU - Jian, Ru-In AU - Jian RI AD - Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Tsao, Li-Yi AU - Tsao LY AD - Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chen, Po-An AU - Chen PA AD - Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chang, Fang-Rong AU - Chang FR AUID- ORCID: 0000-0003-2549-4193 AD - Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Cheng, Yuan-Bin AU - Cheng YB AUID- ORCID: 0000-0001-6581-1320 AD - Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Hu, Hao-Chun AU - Hu HC AD - Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chang, Hsueh-Wei AU - Chang HW AUID- ORCID: 0000-0003-0068-2366 AD - Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. AD - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. LA - eng GR - MOST 108-2320-B-037-015-MY3, MOST 108-2314-B-037-020, MOST 108-2628-B-037-001/Ministry of Science and Technology, Taiwan/ GR - #NSYSUKMU 109-I002/National Sun Yat-sen University-KMU Joint Research Project/ GR - KMUH108-8R67/Kaohsiung Medical University Chung-Ho Memorial Hospital/ GR - KMU-TC108A04/Kaohsiung Medical University Research Center/ GR - MOHW109-TDU-B-212-134016/Health and welfare surcharge of tobacco products, the Ministry of Health and Welfare, Taiwan, Republic of China/ PT - Journal Article DEP - 20200803 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC7465944 OTO - NOTNLM OT - DNA damage OT - apoptosis OT - lichen OT - natural product OT - oxidative stress OT - preferential killing COIS- The authors declare no conflict of interest. EDAT- 2020/08/07 06:00 MHDA- 2020/08/07 06:01 PMCR- 2020/08/03 CRDT- 2020/08/07 06:00 PHST- 2020/06/22 00:00 [received] PHST- 2020/07/13 00:00 [revised] PHST- 2020/07/29 00:00 [accepted] PHST- 2020/08/07 06:00 [entrez] PHST- 2020/08/07 06:00 [pubmed] PHST- 2020/08/07 06:01 [medline] PHST- 2020/08/03 00:00 [pmc-release] AID - antiox9080694 [pii] AID - antioxidants-09-00694 [pii] AID - 10.3390/antiox9080694 [doi] PST - epublish SO - Antioxidants (Basel). 2020 Aug 3;9(8):694. doi: 10.3390/antiox9080694.