Faculty Collaboration Database

Induction of apoptosis by parthenolide in human oral cancer cell lines and tumor xenografts. Oral Oncol 2015 Jun;51(6):602-9

Date

03/31/2015

Pubmed ID

25817195

DOI

10.1016/j.oraloncology.2015.03.003

Scopus ID

2-s2.0-84929130431 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

OBJECTIVES: Parthenolide (PTL), a representative sesquiterpene lactone that is responsible for medicinal properties of the feverfew, is known to modulate diverse intracellular signaling pathways, thereby exerting the tumor growth-inhibitory effects. In this study, authors attempted to examine the pro-apoptotic effects and possible biochemical mechanisms of PTL in human oral cancer cell lines and tumor xenografts.

MATERIAL AND METHODS: The apoptotic effects and related molecular mechanisms of PTL on oral cancer were evaluated using cell viability assay, MTS assay, DAPI staining, western blot analysis, reverse transcriptase-polymerase chain reaction, small interfering RNA transfection and nude mouse xenograft assay.

RESULTS: PTL treatment increased the cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP), and the nuclear fragmentation in a concentration- or time-dependent manner. PTL treatment increased Bim protein expression by enhancing the Bim mRNA expression as well as stabilizing Bim protein level. PTL treatment also induced the translocation of cytosolic Bim into the mitochondria and, more importantly, PTL-induced apoptosis was significantly attenuated, when the Bim expression was knockdown by siRNA transfection. PTL treatment also induced death receptor 5 (DR5) protein expression and this event was closely correlated with an increase in the cleavage of caspase-8 and formation of truncation of Bid (t-Bid). Finally, PTL shrunk tumor size and volume resulting from apoptotic cell death by increasing Bim and DR5 whereas there were no abnormal histopathological findings in normal organs.

CONCLUSION: This study proposes that PTL is a strong apoptotic inducer that deserves the further investigations for potential chemotherapeutic agent of human oral cancers.

Author List

Yu HJ, Jung JY, Jeong JH, Cho SD, Lee JS

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Inflammatory Agents, Non-Steroidal
Apoptosis
Apoptosis Regulatory Proteins
BH3 Interacting Domain Death Agonist Protein
Bcl-2-Like Protein 11
Caspase 3
Caspase 8
Cell Line, Tumor
Female
Humans
Membrane Proteins
Mice
Mice, Nude
Mitochondria
Mouth Neoplasms
Poly(ADP-ribose) Polymerases
Proto-Oncogene Proteins
RNA, Messenger
RNA, Small Interfering
Receptors, TNF-Related Apoptosis-Inducing Ligand
Sesquiterpenes