# Discovery of piperlongumine as a potential novel lead for the development of senolytic agents

Article · Wang Y, Chang J, Liu X, Zhang X, Zhang S, Zhou D, Zheng G

- Archive id: doi:10.18632/aging.101100
- Published: 2016-11-01
- Venue: Aging
- DOI: https://doi.org/10.18632/aging.101100
- PMID: 27913811
- PMCID: PMC5191878
- Citations: 214
- Source URL: https://doi.org/10.18632/aging.101100
- PDF: https://europepmc.org/articles/PMC5191878/pdf
- Provenance: europepmc

## Abstract

Accumulating evidence indicates that senescent cells play an important role in many age-associated diseases. The pharmacological depletion of senescent cells (SCs) with a "senolytic agent", a small molecule that selectively kills SCs, is a potential novel therapeutic approach for these diseases. Recently, we discovered ABT-263, a potent and highly selective senolytic agent, by screening a library of rationally-selected compounds. With this screening approach, we also identified a second senolytic agent called piperlongumine (PL). PL is a natural product that is reported to have many pharmacological effects, including anti-tumor activity. We show here that PL preferentially killed senescent human WI-38 fibroblasts when senescence was induced by ionizing radiation, replicative exhaustion, or ectopic expression of the oncogene Ras . PL killed SCs by inducing apoptosis, and this process did not require the induction of reactive oxygen species. In addition, we found that PL synergistically killed SCs in combination with ABT-263, and initial structural modifications to PL identified analogs with improved potency and/or selectivity in inducing SC death. Overall, our studies demonstrate that PL is a novel lead for developing senolytic agents.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

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