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Article: Biochemical mechanisms of bornyl caffeate induced cytotoxicity in rat pheochromocytoma PC12 cells

TitleBiochemical mechanisms of bornyl caffeate induced cytotoxicity in rat pheochromocytoma PC12 cells
Authors
Issue Date2014
Citation
Chemico-Biological Interactions, 2014, v. 219, p. 133-142 How to Cite?
AbstractThe chemopreventive and antineoplastic activities of caffeic acid derivatives are highly dependent on the chemical structures and cancer cell types. The objective of the present study was to investigate the cytotoxicity of bornyl caffeate and the underlying molecular mechanisms in rat pheochromocytoma PC12 cells. Our initial studies demonstrated that bornyl caffeate exhibited potent cytotoxicity in PC12 cells in a concentration- and time-dependent manner. By examining the cell morphology on a fluorescence microscope and detecting the cell surface phosphoserine with Annexin V-FITC, we proposed that bornyl caffeate could induce apoptosis in PC12 cells. We tested this hypothesis by investigating the effects of bornyl caffeate on several apoptosis-related biomarkers. These experiments showed that bornyl caffeate induced the up-regulation of Bax and down-regulation of Bcl-xl, the disruption of mitochondrial membrane potential, the activation of caspase 3 and the cleavage of PARP. Mechanistic studies further revealed that bornyl caffeate caused the depletion of glutathione (GSH), generation of superoxide ion and progressive activation of p38 mitogen-activate protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in a concentration-dependent manner. In particular, GSH depletion appeared to be the most important mechanism underlying the cytotoxicity of bornyl caffeate. The preservation of the intracellular GSH contents with N-acetyl-l-cysteine (NAC), GSH and vitamin C abolished the effect of bornyl caffeate on the activation of p38 MAPK and JNK, preserved the integrity of mitochondrial membrane and ultimately rescued the cells from drug-induced cell death. These results suggest that bornyl caffeate induces apoptosis in PC12 cells via stimulating the depletion of GSH, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial transmembrane potential.
Persistent Identifierhttp://hdl.handle.net/10722/198261

 

DC FieldValueLanguage
dc.contributor.authorYANG, Cen_US
dc.contributor.authorZHAO, Jen_US
dc.contributor.authorPei, WJen_US
dc.contributor.authorZheng, XHen_US
dc.contributor.authorRong, Jen_US
dc.date.accessioned2014-06-25T02:58:01Z-
dc.date.available2014-06-25T02:58:01Z-
dc.date.issued2014en_US
dc.identifier.citationChemico-Biological Interactions, 2014, v. 219, p. 133-142en_US
dc.identifier.urihttp://hdl.handle.net/10722/198261-
dc.description.abstractThe chemopreventive and antineoplastic activities of caffeic acid derivatives are highly dependent on the chemical structures and cancer cell types. The objective of the present study was to investigate the cytotoxicity of bornyl caffeate and the underlying molecular mechanisms in rat pheochromocytoma PC12 cells. Our initial studies demonstrated that bornyl caffeate exhibited potent cytotoxicity in PC12 cells in a concentration- and time-dependent manner. By examining the cell morphology on a fluorescence microscope and detecting the cell surface phosphoserine with Annexin V-FITC, we proposed that bornyl caffeate could induce apoptosis in PC12 cells. We tested this hypothesis by investigating the effects of bornyl caffeate on several apoptosis-related biomarkers. These experiments showed that bornyl caffeate induced the up-regulation of Bax and down-regulation of Bcl-xl, the disruption of mitochondrial membrane potential, the activation of caspase 3 and the cleavage of PARP. Mechanistic studies further revealed that bornyl caffeate caused the depletion of glutathione (GSH), generation of superoxide ion and progressive activation of p38 mitogen-activate protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in a concentration-dependent manner. In particular, GSH depletion appeared to be the most important mechanism underlying the cytotoxicity of bornyl caffeate. The preservation of the intracellular GSH contents with N-acetyl-l-cysteine (NAC), GSH and vitamin C abolished the effect of bornyl caffeate on the activation of p38 MAPK and JNK, preserved the integrity of mitochondrial membrane and ultimately rescued the cells from drug-induced cell death. These results suggest that bornyl caffeate induces apoptosis in PC12 cells via stimulating the depletion of GSH, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial transmembrane potential.en_US
dc.languageengen_US
dc.relation.ispartofChemico-Biological Interactionsen_US
dc.titleBiochemical mechanisms of bornyl caffeate induced cytotoxicity in rat pheochromocytoma PC12 cellsen_US
dc.typeArticleen_US
dc.identifier.emailRong, J: jrong@hku.hken_US
dc.identifier.authorityRong, J=rp00515en_US
dc.identifier.doi10.1016/j.cbi.2014.05.018en_US
dc.identifier.hkuros229445en_US
dc.identifier.volume204en_US

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