1. Academic Validation
  2. Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway

Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway

  • Molecules. 2017 Sep 11;22(9):1525. doi: 10.3390/molecules22091525.
Liang Ma 1 Yindi Zhu 2 Sheng Fang 3 Hongyan Long 4 Xiang Liu 5 Zi Liu 6
Affiliations

Affiliations

  • 1 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
  • 2 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
  • 3 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
  • 4 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
  • 5 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
  • 6 Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243002, Anhui, China. [email protected].
Abstract

Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits Anticancer influences in several human malignancies. However, the effects and action mechanisms of arenobufagin on non-small-cell lung Cancer (NSCLC) are still unknown. In this study, we reported that arenobufagin acted through activation of Noxa-related pathways and promoted apoptotic cell death in human NSCLC cells. Our results revealed that arenobufagin-induced Apoptosis was caspase-dependent, as evidenced by the fact that caspase-9, Caspase-3 and poly (ADP-ribose) polymerase (PARP) were cleaved, and pretreatment with a pan-caspase inhibitor Z-VAD-FMK inhibited the pro-apoptosis effect of arenobufagin. Mechanistically, we further found that arenobufagin rapidly upregulated the expression of the pro-apoptosis protein Noxa, and abrogated the anti-apoptosis protein Mcl-1, a major binding partner of Noxa in the cell. More importantly, the knockdown of Noxa greatly blocked arenobufagin-induced cell death, highlighting the contribution of this protein in the anti-NSCLC effects of arenobufagin. Interestingly, arenobufagin also increased the expression of p53, a direct transcriptional activator for the upregulation of the Noxa protein. Taken together, our results suggest that arenobufagin is a potential anti-NSCLC agent that triggers apoptotic cell death in NSCLC cells through interfering with the Noxa-related pathway.

Keywords

Mcl-1; Noxa; arenobufagin; non-small-cell lung cancer; p53.

Figures
Products