cytochrome-c-t and Small-Cell-Lung-Carcinoma

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 µg/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.

Topics: Antioxidants; Apoptosis; Apoptosis Inducing Factor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cytochromes c; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Reactive Oxygen Species; Resveratrol; Signal Transduction; Small Cell Lung Carcinoma

The aim of the present study was to evaluate the effects of resveratrol on small-cell lung cancer (SCLC) cell proliferation and apoptosis. The results demonstrated that resveratrol concentration- and time-dependently reduced H446 cell viability. In addition, cells treated with resveratrol displayed higher apoptotic rates, in association with mitochondrial depolarization, cytochrome c release from the mitochondrial compartment to the cytoplasm, apoptosis-inducing factor translocation from the mitochondrial compartment to the nucleus, and altered protein levels of Bcl-2, Bcl-xL and Bax. Furthermore, resveratrol promoted H446 cell inhibition by cisplatin, as reflected by reduced viability and increased apoptosis. These findings suggest that resveratrol exerts antitumor effects on SCLC H446 cells and promotes H446 cell killing by cisplatin via modulation of intrinsic apoptosis.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Inducing Factor; bcl-2-Associated X Protein; bcl-X Protein; Cell Line, Tumor; Cisplatin; Cytochromes c; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Resveratrol; Small Cell Lung Carcinoma

The suillin isoform iso-suillin is a natural substance isolated from a petroleum ether extract of the fruiting bodies of the mushroom Suillus flavus. Previous studies have found its inhibition effect on some cancer cells, and we aimed to study its effects on human small cell lung cancer H446 cell line.. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cellular morphological changes (apoptosis and necrosis) were evaluated using an electron microscope and Hoechst 33258 staining detected by the inverted microscope. Flow cytometry was used to detect cell apoptosis, cell cycle distribution, and mitochondrial membrane potential. Protein expression was determined by Western blotting analysis.. Here, we describe the ability of iso-suillin to inhibit the growth of H446 cells in time- and dose-dependent way. Iso-suillin had no obvious impact on normal human lymphocyte proliferation at low concentrations (9.09, 18.17, or 36.35 μmol/L) but promoted lymphocyte proliferation at a high concentration (72.70 μmol/L). After treatment of different concentrations of iso-suillin (6.82, 13.63, or 20.45 μmol/L), the apoptosis rate of H446 cells increased with increasing concentrations of iso-suillin (16.70%, 35.54%, and 49.20%, respectively, all P < 0.05 compared with the control), and the expression of related apoptotic proteins in the mitochondrial pathway including cytochrome c and caspase-9 were up-regulated compared with the control (all P < 0.05). On the contrary, Bcl-2/Bax ratio was down-regulated compared with the control. Besides, the expression of pro-apoptotic proteins in the death receptor apoptosis pathway, including Fas-associating protein with a novel death domain and caspase-8, and the expression of caspase-3, a downstream regulatory protein of apoptosis, were also increased compared with the control (all P < 0.05). Inhibitors of caspase-9 and caspase-8 reversed the apoptosis process in H446 cells to varying degrees.. These results suggest that iso-suillin could induce H446 cell apoptosis through the mitochondrial pathway and the death-receptor pathway. Therefore, iso-suillin might have a potential application as a novel drug for lung cancer treatment.

Topics: Animals; Apoptosis; Caspase 3; Caspase 8; Caspase 9; Cell Line, Tumor; Cell Survival; Cytochromes c; Diterpenes; Flow Cytometry; Humans; Mice; Phenols; Small Cell Lung Carcinoma