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Abstract Title:

Punicalagin induces senescent growth arrest in human papillary thyroid carcinoma BCPAP cells via NF-κB signaling pathway.

Abstract Source:

Biomed Pharmacother. 2018 Apr 17 ;103:490-498. Epub 2018 Apr 17. PMID: 29677534

Abstract Author(s):

Xian Cheng, Xin Yao, Shichen Xu, Jie Pan, Huixin Yu, Jiandong Bao, Haixia Guan, Rongrong Lu, Li Zhang

Article Affiliation:

Xian Cheng

Abstract:

Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma. Our previous study revealed that punicalagin (PUN), an active component from pomegranate, triggered autophagic cell death and DNA damage response (DDR) in papillary thyroid carcinoma BCPAP cells. But the detailed anti-cancer mechanisms of punicalagin against PTC still remained to be further explored. DDR activation is a proven cause of cellular senescence, which mediates anti-tumor processes under certain circumstances. In this study, we reported that punicalagin treatment generated a senescent phenotype of BCPAP cells characterized as altered morphology, increased cell granularity and senescence-associatedβ-galactosidase (SA-β-Gal) staining. Senescence induced by punicalagin treatment was further confirmed by cell cycle arrest and upregulation of cyclin-dependent kinase inhibitor p21. Meanwhile, the senescence-associated secretory phenotype (SASP) included high levels of inflammatory cytokines, principally IL-6 and IL-1β. Furthermore, punicalagin exposure caused the phosphorylation and subsequent degradation of IκBα as well as the nuclear translocation of p65, suggesting the activation of NF-κB signaling pathway. Inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, partially reversed the cellular senescent phenotype induced by punicalagin in BCPAP cells as evidenced by the decreased fraction of SA-β-Gal staining positive cells and blockage of SASP generation. These results collectively showed that punicalagin treatment induced senescent growth arrest and SASP via triggering NF-κB activation. These observations elucidated novel anti-cancer mechanisms of punicalagin and might provide new potential prospects for PTC therapy.

Study Type : In Vitro Study

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