School of Medicine Publications and Presentations

Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: involvement of glucose import, ROS, NF-κB and lncRNAs

Document Type

Article

Publication Date

2-4-2022

Abstract

Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) roots. Originally discovered in 1961, the biological activities of this molecule against some cancer types was reported during the last decade. Whether PL can synergize with doxorubicin and the underlying mechanism in breast cancer remains elusive. Herein, we report the activities of PL in numerous breast cancer cell lines. PL reduced the migration and colony formation by cancer cells. An enhancement in the sub-G1 population, reduction in the mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the cell survival proteins was observed by the alkaloid. Further, PL induced ROS generation in breast cancer cells. While TNF-α induced p65 nuclear translocation, PL suppressed the translocation in cancer cells. The expression of lncRNAs such as MEG3, GAS5 and H19 were also modulated by the alkaloid. The molecular docking studies revealed that PL can interact with both p65 and p50 subunits. PL reduced the glucose import and altered the pH of the medium towards the alkaline side. PL also suppressed the expression of glucose and lactate transporter in breast cancer cells. In tumor bearing mouse model, PL was found to synergize with doxorubicin and reduced the size, volume and weight of the tumor. Overall, the effects of doxorubicin in cancer cells are enhanced by PL. The modulation of glucose import, NF-κB activation and lncRNAs expression may have contributory role for the activities of PL in breast cancer.

Comments

Copyright © 2022, The Author(s), under exclusive licence to Springer Science Business Media, LLC, part of Springer Nature

https://rdcu.be/cNUFS

Publication Title

Apoptosis

DOI

10.1007/s10495-022-01711-6

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology

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