Open Access

Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy

  • Authors:
    • Linhai Zhu
    • Ying Wang
    • Wang Lv
    • Xiao Wu
    • Hongxu Sheng
    • Cheng He
    • Jian Hu
  • View Affiliations

  • Published online on: October 12, 2021     https://doi.org/10.3892/ijmm.2021.5047
  • Article Number: 214
  • Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Schizandrin A (SchA) can be extracted from the vine plant Schisandra chinensis and has been reported to confer various biologically active properties. However, its potential biological effects on non‑small cell lung cancer (NSCLC) remain unknown. Therefore, the present study aims to address this issue. NSCLC and normal lung epithelial cell lines were first treated with SchA. Cell viability and proliferation were measured using CellTiter‑Glo Assay and colony formation assays, respectively. PI staining was used to measure cell cycle distribution. Cell cycle‑related proteins p53, p21, cyclin D1, CDK4, CDK6, cyclin E1, cyclin E2, CDK2 and DNA damage‑related protein SOX4 were detected by western blot analysis. Annexin V‑FITC/PI staining, DNA electrophoresis and Hoechst 33342/PI dual staining were used to detect apoptosis. JC‑1 and DCFH‑DA fluorescent dyes were used to measure the mitochondrial membrane potential and reactive oxygen species concentrations, respectively. Apoptosis‑related proteins caspase‑3, cleaved caspase‑3, poly(ADP‑ribose) polymerase (PARP), cleaved PARP, BimEL, BimL, BimS, Bcl2, Bax, caspase‑9 and cleaved caspas‑9 were measured by western blot analysis. Dansylcadaverine was used to detect the presence of the acidic lysosomal vesicles. The expression levels of the autophagy‑related proteins LC3‑I/II, p62/SQSTM and AMPKα activation were measured using western blot analysis. In addition, the autophagy inhibitor 3‑methyladenine was used to inhibit autophagy. SchA treatment was found to reduce NSCLC cell viability whilst inhibiting cell proliferation. Low concentrations of SchA (10‑20 µM) mainly induced G1/S‑phase cell cycle arrest. By contrast, as the concentration of SchA used increases (20‑50 µM), cells underwent apoptosis and G2/M‑phase cell cycle a13rrest. As the treatment concentration of SchA increased from 0 to 50 µM, the expression of p53 and SOX4 protein also concomitantly increased, but the expression of p21 protein was increased by 10 µM SchA and decreased by higher concentrations (20‑50 µM). In addition, the mRNA and protein expression levels of Bcl‑like 11 (Bim)EL, BimL and BimS increased following SchA application. SchA induced the accumulation of acidic vesicles and induced a marked increase in the expression of LC3‑II protein, suggsting that SchA activated the autophagy pathway. However, the expression of the p62 protein was found to be increased by SchA, suggesting that p62 was not degraded during the autophagic flux. The 3‑methyladenine exerted no notable effects on SchA‑induced apoptosis. Taken together, results from the present study suggest that SchA exerted inhibitory effects on NSCLC physiology by inducing cell cycle arrest and apoptosis. In addition, SchA partially induced autophagy, which did not result in any cytoprotective effects.

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December-2021
Volume 48 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhu L, Wang Y, Lv W, Wu X, Sheng H, He C and Hu J: Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy. Int J Mol Med 48: 214, 2021
APA
Zhu, L., Wang, Y., Lv, W., Wu, X., Sheng, H., He, C., & Hu, J. (2021). Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy. International Journal of Molecular Medicine, 48, 214. https://doi.org/10.3892/ijmm.2021.5047
MLA
Zhu, L., Wang, Y., Lv, W., Wu, X., Sheng, H., He, C., Hu, J."Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy". International Journal of Molecular Medicine 48.6 (2021): 214.
Chicago
Zhu, L., Wang, Y., Lv, W., Wu, X., Sheng, H., He, C., Hu, J."Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy". International Journal of Molecular Medicine 48, no. 6 (2021): 214. https://doi.org/10.3892/ijmm.2021.5047