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.
Highlights
Lung cancer continues to be the most common cause of cancer death in the world, responsible for nearly one cancer death in five [1]
The results showed that arenobufagin exhibited higher activity to A549, NCI-H460 and NCI-H1975 non-small-cell lung cancer (NSCLC) cells, with IC50 values around 10 nM
Thereafter, we systematically evaluated the effect of arenobufagin on A549 and NCI-H460 cells with lower IC50 values (Figure 1B)
Summary
Lung cancer continues to be the most common cause of cancer death in the world, responsible for nearly one cancer death in five [1]. Non-small-cell lung cancer (NSCLC), which primarily includes adenocarcinoma and squamous cell carcinoma, accounts for approximately 85% of all cases of lung cancer. Despite advances in early detection, NSCLC is often diagnosed at an advanced stage, or a locally advanced stage. Chemotherapeutic agents have provided the standard regimen backbone for these patients, as well as combination chemotherapy. As a result of resistance, the prognosis for NSCLC patients is still poor, with a 5-year survival rate of less than 15% [2,3]. There is an urgent need to develop more effective therapies for NSCLC patients
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
