Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

Abstract

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.

Effect of Hydroalcoholic Extract of Ephedra major, Momordica charantia, and Resveratrol on Cytotoxicity and Caspase-3 Genes Expression Level in MCF-7 Breast Cancer Cell Line

“…The effect of resveratrol on cell proliferation is not similar in all breast cancer cell lines (25). The efficiency of resveratrol for 50% growth inhibition of H446 cancer cells was determined at 40 µg/mL resveratrol concentration (26), while in this work, the MCF-7 cell growth inhibition was observed at 75 µg/mL of resveratrol.…”

Resveratrol Can Attenuate Astrocyte Activation to Treat Spinal Cord Injury by Inhibiting Inflammatory Responses

“… Neuroprotective Anti-inflammatory Anti-apoptosis [ 49 ] Cancer Lung cancer (LC) Human small-cell LC (SCLC) H446 cell line H446 cells were cultured in media with RSV (40 µg/ml) RSV inhibited the survival of human SCLC H446 cells, and promoted apoptosis by inhibiting PI3K/Akt/c-Myc signaling pathway. Anticancer Antioxidant [ 50 ] Pancreatic cancer (PC) Human pancreatic stellate cells (PSCs)/ KPC mice PSCs were cultured in media with 50 µM RSV/ KPC mice were treated with 50 mg/kg RSV RSV blocked the interaction between PSCs and PC cells, and thus inhibited malignant proliferation of PC cells by inhibiting the activation of hypoxia-induced PSCs. Anticancer Antioxidant [ 51 ] Colon cancer Human colon cancer cell lines SW480 and SW620/ BalB/c (nu/nu) mice SW480 and SW620 cells transfected with siAKT1 were established in EMT model by using epidermal growth factor.…”

Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways

“…Antioxidants are proposed to exhibit anticancer roles by interfering with the tumor microenvironment. Resveratrol is a natural antioxidant and affects cellular oxidative stress and mitochondrial membrane potential by interfering with the PI3K/Akt signaling pathway in SCLC H446 cell lines ( Li et al, 2020 ). In another study conducted by Jiao and collaborators (2015), resveratrol inhibited invasive behaviors in vitro and in vivo by PI3K/Akt/NF-κB suppression and the inhibition of MMP-2 secretion in glioblastoma ( Jiao et al, 2015 ).…”