PMID- 30720102 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20190624 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 41 IP - 4 DP - 2019 Apr TI - Autophagy and apoptotic machinery caused by Polygonum cuspidatum extract in cisplatin‑resistant human oral cancer CAR cells. PG - 2549-2557 LID - 10.3892/or.2019.6985 [doi] AB - Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti‑angiogenesis, anti‑human immunodeficiency virus (HIV), anti‑hepatitis B virus, anti‑microbial, anti‑inflammatory, and neuro‑protective bio‑activities. However, the effect of P. cuspidatum extract (PCE) on drug‑resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE‑treated cisplatin‑resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration‑ and time‑dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3‑GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6‑diamidino‑2‑phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL) double staining. PCE significantly stimulated caspase‑9 and ‑3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin‑1, LC3, Bax and cleaved caspase‑3, while it decreased the protein expression of Bcl‑2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin‑resistant human oral cancer. FAU - Wang, Yin-Lai AU - Wang YL AD - Department of Dentistry, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan, R.O.C. FAU - Horng, Chi-Ting AU - Horng CT AD - Department of Ophthalmology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan, R.O.C. FAU - Hsieh, Min-Tsang AU - Hsieh MT AD - School of Pharmacy, China Medical University, Taichung 40402, Taiwan, R.O.C. FAU - Chen, Hung-Che AU - Chen HC AD - Department of Pharmacy and Master Program, Tajen University, Pingtung 90741, Taiwan, R.O.C. FAU - Huang, Yu-Syuan AU - Huang YS AD - Department of Pharmacy and Master Program, Tajen University, Pingtung 90741, Taiwan, R.O.C. FAU - Yang, Jai-Sing AU - Yang JS AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan, R.O.C. FAU - Wang, Guo-Kai AU - Wang GK AD - School of Pharmacy, Anhui University of Chinese Medicine, Anhui Key Lab of Modern Chinese Materia Medica, Hefei, Anhui 230012, P.R. China. FAU - Chiang, Jo-Hua AU - Chiang JH AD - Department of Nursing, Chung Jen Catholic Junior College, Chiayi 62241, Taiwan, R.O.C. FAU - Chen, Hul-Han AU - Chen HH AD - Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 275297, USA. FAU - Lu, Chi-Cheng AU - Lu CC AD - Department of Sport Performance, National Taiwan University of Sport, Taichung 40404, Taiwan, R.O.C. FAU - Chen, Fu-An AU - Chen FA AD - Department of Pharmacy and Master Program, Tajen University, Pingtung 90741, Taiwan, R.O.C. LA - eng PT - Journal Article DEP - 20190128 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Antineoplastic Agents) RN - 0 (Plant Extracts) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Apoptosis/drug effects MH - Autophagy/drug effects MH - Cell Line, Tumor MH - Cisplatin/*pharmacology/therapeutic use MH - Drug Resistance, Neoplasm MH - Drug Screening Assays, Antitumor MH - Fallopia japonica/*chemistry MH - Humans MH - Mouth Neoplasms/*drug therapy/pathology MH - Plant Extracts/*pharmacology/therapeutic use MH - Signal Transduction/drug effects EDAT- 2019/02/06 06:00 MHDA- 2019/06/25 06:00 CRDT- 2019/02/06 06:00 PHST- 2018/09/28 00:00 [received] PHST- 2019/01/04 00:00 [accepted] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2019/02/06 06:00 [entrez] AID - 10.3892/or.2019.6985 [doi] PST - ppublish SO - Oncol Rep. 2019 Apr;41(4):2549-2557. doi: 10.3892/or.2019.6985. Epub 2019 Jan 28.