PMID- 25904129 OWN - NLM STAT- MEDLINE DCOM- 20160606 LR - 20150916 IS - 1432-0614 (Electronic) IS - 0175-7598 (Linking) VI - 99 IP - 20 DP - 2015 Oct TI - The role of autophagy in the cytotoxicity induced by recombinant human arginase in laryngeal squamous cell carcinoma. PG - 8487-94 LID - 10.1007/s00253-015-6565-6 [doi] AB - Laryngeal squamous cell carcinoma (LSCC), one of the most common malignant solid tumors in the world, has a high rate of mortality, recurrence, and metastasis. Recombinant human arginase (rhArg) recently has been developed in arginine deprivation therapy for a number of malignant tumors. In the present study, we observed that rhArg triggered significant cytotoxicity in human laryngeal squamous cell carcinoma Tu212 cells. Meanwhile, we observed that rhArg simultaneously activated autophagic flux in Tu212 cells, which was demonstrated by the accumulation of autophagosome and light chain 3 II (LC3-II). And, we explored the role of autophagy in cytotoxicity induced by rhArg in Tu212 cells. Autophagy inhibitors including chloroquine (CQ) and bafilomycin A1 (Baf A1) enhanced cytotoxicity induced by rhArg, implying the protective role of autophagy in rhArg-treated Tu212 cells. Moreover, Akt/mTOR signaling pathway was most possibly to participate in the rhArg-induced autophagy. Meanwhile, rhArg could upregulate the phosphorylation of ERK1/2 in a time-dependent manner. Therefore, all the results illuminated the cytoprotective role of autophagy in the treatment of rhArg in laryngeal squamous carcinoma Tu212 cells and provided a potential approach for LSCC therapy by rhArg combined with autophagy inhibitors. FAU - Lin, Chen AU - Lin C AD - Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. FAU - Wang, Ziyu AU - Wang Z AD - Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China. AD - Department of Biopharmaceutical Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China. FAU - Li, Li AU - Li L AD - Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. FAU - He, Yong AU - He Y AD - Department of Otolaryngology, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang Province, China. FAU - Fan, Jiajun AU - Fan J AD - Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China. FAU - Liu, Zhongyu AU - Liu Z AD - Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. FAU - Zhao, Shuwei AU - Zhao S AD - Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. 13621671816@163.com. FAU - Ju, Dianwen AU - Ju D AD - Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China. dianwenju@fudan.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150423 PL - Germany TA - Appl Microbiol Biotechnol JT - Applied microbiology and biotechnology JID - 8406612 RN - 0 (Recombinant Proteins) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Arginase/genetics/*toxicity MH - Autophagy/*drug effects MH - Cell Line, Tumor MH - Cell Survival/*drug effects MH - Epithelial Cells/*drug effects/*physiology MH - Humans MH - Recombinant Proteins/genetics/toxicity OTO - NOTNLM OT - Autophagy OT - Cytotoxicity OT - Laryngeal squamous cell carcinoma OT - Recombinant human arginase EDAT- 2015/04/24 06:00 MHDA- 2016/06/09 06:00 CRDT- 2015/04/24 06:00 PHST- 2015/01/10 00:00 [received] PHST- 2015/03/20 00:00 [accepted] PHST- 2015/03/20 00:00 [revised] PHST- 2015/04/24 06:00 [entrez] PHST- 2015/04/24 06:00 [pubmed] PHST- 2016/06/09 06:00 [medline] AID - 10.1007/s00253-015-6565-6 [pii] AID - 10.1007/s00253-015-6565-6 [doi] PST - ppublish SO - Appl Microbiol Biotechnol. 2015 Oct;99(20):8487-94. doi: 10.1007/s00253-015-6565-6. Epub 2015 Apr 23.