PMID- 32901891 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210921 IS - 1791-2431 (Electronic) IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 44 IP - 5 DP - 2020 Nov TI - Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway. PG - 1821-1830 LID - 10.3892/or.2020.7747 [doi] AB - There have been no major breakthroughs in the treatment of small‑cell lung cancer (SCLC) in recent decades. It is thus essential to explore new or adjuvant treatment options for SCLC. Resveratrol (Res) is a natural antioxidant revealed to influence the entire process of cancer development. Accordingly, the present study used the SCLC cell line H446 to explore the antitumor mechanism of Res. Cells were treated with 40 microg/ml Res with or without pretreatment with the antioxidant N‑acetyl‑L‑cysteine (NAC). H446 cell viability and apoptosis were assessed with MTT and flow cytometry, and the expression of cytochrome c and the PI3K/Akt/c‑Myc pathway and the nuclear translocation of apoptosis inducing factor (AIF) were assessed by western blotting. In addition, the changes in ROS content and mitochondrial membrane potential were determined. The results revealed that Res inhibited H446 cell viability and induced apoptosis, increased cytochrome c expression, inhibited the expression of PI3K/Akt/c‑Myc signaling pathway components, and promoted the translocation of AIF from the cytoplasm to the nucleus in H446 cells. However, NAC pretreatment reversed these changes to various extents. The results of the present study indicated that Res may inhibit the viability and promote the apoptosis of human SCLC H446 cells through the PI3K/Akt/c‑Myc pathway and that oxidative stress and mitochondrial membrane potential depolarization may be involved in the aforementioned processes. FAU - Li, Wangping AU - Li W AD - Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710038, P.R. China. FAU - Li, Chunmei AU - Li C AD - Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710038, P.R. China. FAU - Ma, Lijie AU - Ma L AD - Department of Pulmonary and Critical Care Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China. FAU - Jin, Faguang AU - Jin F AD - Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710038, P.R. China. LA - eng PT - Journal Article DEP - 20200901 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Antioxidants) RN - 0 (Apoptosis Inducing Factor) RN - 0 (MYC protein, human) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (Reactive Oxygen Species) RN - 9007-43-6 (Cytochromes c) RN - EC 2.7.11.1 (AKT1 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - Q369O8926L (Resveratrol) SB - IM MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - Apoptosis Inducing Factor/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Cytochromes c/metabolism MH - Humans MH - Lung Neoplasms/*drug therapy/metabolism/pathology MH - Membrane Potential, Mitochondrial/drug effects MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism MH - Proto-Oncogene Proteins c-myc/antagonists & inhibitors/*metabolism MH - Reactive Oxygen Species/metabolism MH - Resveratrol/*pharmacology MH - Signal Transduction/drug effects MH - Small Cell Lung Carcinoma/*drug therapy/metabolism/pathology PMC - PMC7550979 OTO - NOTNLM OT - resveratrol OT - small-cell lung cancer OT - PI3K/Akt/c-Myc pathways EDAT- 2020/09/10 06:00 MHDA- 2021/07/20 06:00 PMCR- 2020/09/01 CRDT- 2020/09/09 08:47 PHST- 2019/11/20 00:00 [received] PHST- 2020/05/06 00:00 [accepted] PHST- 2020/09/10 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2020/09/09 08:47 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - or-44-05-1821 [pii] AID - 10.3892/or.2020.7747 [doi] PST - ppublish SO - Oncol Rep. 2020 Nov;44(5):1821-1830. doi: 10.3892/or.2020.7747. Epub 2020 Sep 1.