Effect of Withaferin A on A549 Cellular Proliferation and Apoptosis in Non-small Cell Lung Cancer

  • Cai, Yong (Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Sheng, Zhao-Ying (Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Chen, Yun (Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Bai, Chong (Department of Respiration, Changhai Hospital, Second Military Medical University)
  • Published : 2014.02.28


Objective: To explore the effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC cell line A549 was selected to explore the effect of Withaferin A on A549 cellular proliferation, apoptosis and the PI3K/Akt signal pathway capable of regulating tumor biological behavior by assessment of cellular proliferation, cellular apoptotic rates and cellular cycling as well as by immuno-blotting. Results: Withaferin A could inhibit A549 cellular proliferation and the control rate was dosage-dependent (P<0.05), which also increased time-dependently with the same dosage of Withaferin A (P<0.05). The apoptotic indexes in A549 cells treated with 0, 2.5, 5.0, 10.0 and 20.0 ${\mu}mol{\cdot}L^{-1}$ Withaferin A for 48 h were significantly different (P<0.05). In addition, the apoptotic rates of each group in both early and advanced stages were higher than those in 0 ${\mu}mol{\cdot}L^{-1}$ (P<0.05), which were evidently higher after 48 h than those after 24 h (P<0.05). A549 cells treated by Withaferin A for 48 h were markedly lower in Bcl-2 level and obviously higher in Bax and cleaved caspase-3 levels than those treated by 0 ${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05), and there were significant differences among 5, 10 and 20 ${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05). The ratios of A549 cells treated by Withaferin A for 48 h in G0/G1 stage were higher than those in 0 ${\mu}mol{\cdot}L^{-1}$, while those in S and G2/M stages were obviously lower than those in G2/M stage, and there were significant differences in 5.0, 10.0 and 20.0 ${\mu}mol{\cdot}L^{-1}$ Withaferin A (P<0.05). Additionally, p-Akt/Akt values were in reverse association with dosage, and the differences were significant (P<0.05). Conclusion: Withaferin A can inhibit the proliferation and apoptosis of A549 cells by suppressing activation of the PI3K/Akt pathways.


  1. Wang JY, Cai Y (2013). Clinical observation and prognostic analysis of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 6267-71.
  2. Yan HA, Shen K, Huang XE (2013). Clinical study on mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4801-4.
  3. Yu SM, Kim SJ (2013). Production of reactive oxygen species by withaferin A causes loss of type collagen expression and COX-2 expression through the PI3K/Akt, p38, and JNK pathways in rabbit articular chondrocytes. Exp Cell Res, 319, 2822-34.
  4. Lee DH, Lim IH, Sung EG, et al (2013). Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway. Oncol Rep, 30, 933-8.
  5. Hahm ER, Lee J, Singh SV (2013). Role of mitogen-activated protein kinases and Mcl-1 in apoptosis induction by withaferin A in human breast cancer cells. Mol Carcinog, Epub ahead of print.
  6. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300.
  7. Kim SH, Jang YW, Hwang P, et al (2012). The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats. Exp Mol Med, 44, 45-51.
  8. Li X, Wang M, Tian R, et al (2013). Apoptosis of human gallbladder carcinoma GBC-SD cells induced by withaferin A and its possible mechanism. Tumor, 33, 502-7.
  9. Liu ZG, Yu ZC, Yu YP, et al (2010). Lysophosphatidic acid level and the incidence of silent brain infarction in patients with nonvalvular atrial fibrillation. Int J Mol Sci, 11, 3988-98.
  10. Lu YY1, Huang XE, Cao J (2013). Phase II study on Javanica oil emulsion injection ($Yadanzi^{(R)}$) combined with chemotherapy in treating patients with advanced lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 4791-4.
  11. Osaki M, Oshimura M, Ito H (2004). PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis, 9, 667-76.
  12. Roy RV, Suman S, Das TP, et al (2013). Withaferin a, a steroidal lactone from withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells. J Nat Prod, 76, 1909-15.
  13. Verdecchia A, Francisci S, Brenner H, et al (2007). Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol, 8, 784-96.
  14. Cho KH, Park S, Lee KS (2013). A single measure of cancer burden in Korea from 1999 to 2010. Asian Pac J Cancer Prev, 14, 5249-55.
  15. Hahm ER, Lee J, Kim SH, et al (2013). Metabolic alterations in mammary cancer prevention by withaferin A in a clinically relevant mouse model. J Natl Cancer Inst, 105, 1111-22.

Cited by

  1. Withaferin A induces apoptosis through the generation of thiol oxidation in human head and neck cancer cells vol.35, pp.1, 2014,
  2. Chemotherapeutic Effect of Withaferin A in Human Oral Cancer Cells vol.06, pp.08, 2015,
  3. Inhibitory effect of withaferin A on Helicobacter pylori-induced IL-8 production and NF-κB activation in gastric epithelial cells vol.13, pp.1, 2015,
  4. Current Drugs and Drug Targets in Non-Small Cell Lung Cancer: Limitations and Opportunities vol.16, pp.10, 2015,
  5. Withaferin-A—A Natural Anticancer Agent with Pleitropic Mechanisms of Action vol.17, pp.3, 2016,
  6. Glucocorticoid receptor-mediated delivery of nano gold–withaferin conjugates for reversal of epithelial-to-mesenchymal transition and tumor regression vol.11, pp.19, 2016,
  7. Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis vol.14, pp.1, 2017,
  8. Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells vol.8, pp.1, 2018,