Curcumin potentiates the ErbB receptors inhibitor Afatinib for enhanced antitumor activity in malignant mesothelioma

Abstract

Several attempts have been made to develop targeted therapies for malignant mesothelioma (MM), an aggressive tumour with a poor prognosis. In this study we evaluated whether Curcumin (CUR) potentiated the antitumor activity of the ErbB receptors inhibitor Afatinib (AFA) on MM, employing cell lines cultured in vitro and mice bearing intraperitoneally transplanted, syngeneic MM cells. The rationale behind this hypothesis was that CUR could counteract mechanisms of acquired resistance to AFA. We analysed CUR and AFA effects on MM cell growth, cell cycle, autophagy, and on the modulation of tumour-supporting signalling pathways.

This study demonstrated that, as compared to the individual compounds, the combination of AFA + CUR had a stronger effect on MM progression which can be ascribed either to increased tumour cell growth inhibition or to an enhanced pro-apoptotic effect. These results warrant future studies aimed at further exploring the therapeutic potential of AFA + CUR-based combination regimens for MM treatment.

Keywords:

• Malignant mesothelioma
• afatinib
• curcumin
• EGFR/ErbB receptors
• polyphenols

Acknowledgements

The authors thank Dr. Agnes Kane (Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island) for providing the 40 cell line, and Prof. Antonio Procopio (Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy) for providing human MM cell lines. R.C. is recipient of the Tor Vergata PhD program in Tissue Engineering and Remodeling Biotechnologies for Body Functions. V.A. is recipient of the Sapienza PhD program in Molecular Medicine. B.K. is recipient of the Tor Vergata PhD program in Materials for Health, Environment and Energy.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was funded by a grant from the Ministero dell’Università e della Ricerca, PRIN 2020, [BeiR20Prin, CUP: E85F22000060006, Prot. 20205HZBP8_006 to R.B.] and PRIN 2022 PNRR [Codice progetto: P2022LZXNW to R.B], and grants from the University of Rome “Sapienza” Ateneo 2021 and Ateneo 2022 [RM12117A7F986146 and RM12218166C5057A respectively, to L.M.].