Alantolactone enhances Cisplatin anticancer activity in A549 cells through inhibition of STAT3 activation and mitochondrial dependent pathway

Bashir Ahmad, Mohamed Y. Zaky, Bakhtawar Khan, Akbar Husain, Gehad R. Abdelbaset, Ata Ur Rehman, Zaheer Ud Din, Syed Rafiq Hussain, Mohammed Alshwmi

Abstract


An FDA approved drug Cisplatin (CIS) (Cic-diamminedichloroplatinum [II]; CDDP; Platinol) is an anti-neoplastic which serves as a potential treatment option for the treatment of a variety of cancers and led to improve cure and survival rate.  Alantolactone (ALT) is a sesquiterpene compound derived from Innula helinum and possesses potent anticancer activities against different cancers. The present study was conducted whether the ALT enhance the CIS anticancer activity or not? First we explored the different concentrations of ALT and CIS and found that the ALT at 20 µM could enhance the activity of CIS (80 µM). ALT at 20 µM induced apoptosis and inhibit the growth of A549 cells while CIS (80 µM) failed to inhibit or induced apoptosis in A549 cells while in combination they dramatically increased apoptosis in A549 cells. ALT and CIS in combination inhibit the STAT-3 at tyrosine 705, surviving, Bcl-2, Bclxl and increased the expression of Bax, cleaved (Cl)-caspase-3 and cl-parp and led the A549 cell to apoptosis. Our findings suggest that the ALT and CIS might be a good therapeutic approach to improve the efficacy of CIC in lung adenocarcinoma. 


Keywords


Alantolactone, Cisplatin, STAT-3, Bcl-2, Bclxl

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