PMID- 29533931 OWN - NLM STAT- MEDLINE DCOM- 20180514 LR - 20211204 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 45 IP - 5 DP - 2018 TI - Sepia Ink Oligopeptide Induces Apoptosis of Lung Cancer Cells via Mitochondrial Pathway. PG - 2095-2106 LID - 10.1159/000488046 [doi] AB - BACKGROUND/AIMS: Our previous study suggested the anti-tumor activity of sepia ink oligopeptide (SIO). Here we sought to investigate the underlying molecular mechanism. METHODS: Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by Annexin V/Propidium Iodide (PI) staining. The mitochondria pathway was characterized by quantification of Bcl-2, Bax, Caspase-9 and Cyto-C. The death receptor pathway was analyzed by determinement of Fas, Caspase-8 and NIK. The endoplasmic reticulum (ER)-dependent pathway was determined by measurement the expression of CHOP, Caspase-12, GRP78 and Calpain. The associated gene expression was quantified by RT-PCR and protein level was determined by immunoblotting. RESULTS: We demonstrated treatment with structurally modified SIO (CSIO, 5 microM) significantly inhibited cell proliferation and induced apoptosis in lung cancer cell line A549. The mitochondrial pathway, death receptor pathway and ER stress induced apoptosis were stimulated upon CSIO treatment. The administration with respective inhibitors including midiv-1 (50 microM for 2 h), PDTC (20 microM PDTC for 30 min) and ALLN (20 mM ALLN for 5 h) readily reversed the apoptosis inducing effect of CSIO. CONCLUSION: Our data demonstrates that CSIO is capable of induction apoptosis in lung cancer cell line, which is mediated by all three classical apoptotic pathways. Our results warrant further in vivo investigations of the anti-tumor potential of CSIO. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Wang, Xiaohua AU - Wang X AD - Department of chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Chen, Cheng AU - Chen C AD - Department of Radiotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Zhou, Guoren AU - Zhou G AD - Department of chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Ye, Jinjun AU - Ye J AD - Department of Radiotherapy, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Yin, Rong AU - Yin R AD - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Feng, Dongjie AU - Feng D AD - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Zhang, Shuai AU - Zhang S AD - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Wang, Xiaojun AU - Wang X AD - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. FAU - Zhao, Xin AU - Zhao X AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhang, Zhi AU - Zhang Z AD - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China. LA - eng PT - Journal Article DEP - 20180307 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (DDIT3 protein, human) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (FAS protein, human) RN - 0 (HSPA5 protein, human) RN - 0 (Leupeptins) RN - 0 (Oligopeptides) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Thiocarbamates) RN - 0 (bcl-2-Associated X Protein) RN - 0 (fas Receptor) RN - 110044-82-1 (acetylleucyl-leucyl-norleucinal) RN - 135467-92-4 (prolinedithiocarbamate) RN - 147336-12-7 (Transcription Factor CHOP) RN - 9DLQ4CIU6V (Proline) RN - EC 3.4.22.- (Calpain) RN - EC 3.4.22.- (Caspase 12) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - A549 Cells MH - Animals MH - Apoptosis/*drug effects MH - Calpain/genetics/metabolism MH - Caspase 12/genetics/metabolism MH - Caspase 8/genetics/metabolism MH - Caspase 9/genetics/metabolism MH - Cell Proliferation/drug effects MH - Endoplasmic Reticulum/metabolism MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/drug effects MH - Humans MH - Ink MH - Leupeptins/toxicity MH - Lung Neoplasms/metabolism/pathology MH - Mitochondria/*drug effects/metabolism MH - Oligopeptides/*toxicity MH - Proline/analogs & derivatives/toxicity MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - Sepia/*metabolism MH - Thiocarbamates/toxicity MH - Transcription Factor CHOP/genetics/metabolism MH - bcl-2-Associated X Protein/genetics/metabolism MH - fas Receptor/genetics/metabolism OTO - NOTNLM OT - Apoptosis OT - ER stress OT - Lung cancer OT - Mitochondrial pathway OT - Sepia ink oligopeptide EDAT- 2018/03/14 06:00 MHDA- 2018/05/15 06:00 CRDT- 2018/03/14 06:00 PHST- 2017/07/24 00:00 [received] PHST- 2018/02/02 00:00 [accepted] PHST- 2018/03/14 06:00 [pubmed] PHST- 2018/05/15 06:00 [medline] PHST- 2018/03/14 06:00 [entrez] AID - 000488046 [pii] AID - 10.1159/000488046 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;45(5):2095-2106. doi: 10.1159/000488046. Epub 2018 Mar 7.