Aims: Phenethyl caffeate benzoxanthene lignan (PCBL) is a synthetic compound with DNA interacting,antiangiogenic, antiproliferative and tumor cell death inducing abilities. Though PCBL exhibits the qualitiesof a prospective antitumor agent, the basic mechanism of PCBL induced cell death remains unknown. Thisstudy aims to analyze the molecular mechanisms of PCBL induced cell death in tumor cells to further substantiateits antitumor abilities.Main methods: MTT assay was used for finding cell proliferation inhibition, flow cytometric analysis for thedetection of cell cycle arrest, comet assay for DNA break detection and immunofluorescence for analyzingH2AX phosphorylation. Western blot analysis was used to detect the activation of different proteins relatedto DNA damage response and apoptosis.Key findings: PCBL inhibited proliferation of WiDr cells more efficiently than its analog, MCBL. Comet analysisof PCBL treated WiDr cells and activity of various DNA damage response proteins such as γ-H2AX, BRCA1,ATR and Chk1 in PCBL treated cells demonstrated the DNA damaging property of PCBL. Effector moleculesof apoptosis such as caspase-3, caspase-7 and caspase-9 were found activated along with PARP cleavage inPCBL treated cells, suggesting apoptosis as the main mode of cell death. PCBL induced cell death was foundassociated with the activation of MAPK signaling. Inhibition of ERK, one of the MAPKs, by U0126 improvedthe apoptosis inducing ability of PCBL.Significance: In vitro findings suggest that PCBL works by initiating DNA damage and inducing apoptosis incancer cells and thus could be considered for further preclinical studies

Phenethyl caffeate benzo[kl]xanthene lignan with DNA interacting properties induces DNA damage and apoptosis in colon cancer cells

TRINGALI, Corrado;
2012

Abstract

Aims: Phenethyl caffeate benzoxanthene lignan (PCBL) is a synthetic compound with DNA interacting,antiangiogenic, antiproliferative and tumor cell death inducing abilities. Though PCBL exhibits the qualitiesof a prospective antitumor agent, the basic mechanism of PCBL induced cell death remains unknown. Thisstudy aims to analyze the molecular mechanisms of PCBL induced cell death in tumor cells to further substantiateits antitumor abilities.Main methods: MTT assay was used for finding cell proliferation inhibition, flow cytometric analysis for thedetection of cell cycle arrest, comet assay for DNA break detection and immunofluorescence for analyzingH2AX phosphorylation. Western blot analysis was used to detect the activation of different proteins relatedto DNA damage response and apoptosis.Key findings: PCBL inhibited proliferation of WiDr cells more efficiently than its analog, MCBL. Comet analysisof PCBL treated WiDr cells and activity of various DNA damage response proteins such as γ-H2AX, BRCA1,ATR and Chk1 in PCBL treated cells demonstrated the DNA damaging property of PCBL. Effector moleculesof apoptosis such as caspase-3, caspase-7 and caspase-9 were found activated along with PARP cleavage inPCBL treated cells, suggesting apoptosis as the main mode of cell death. PCBL induced cell death was foundassociated with the activation of MAPK signaling. Inhibition of ERK, one of the MAPKs, by U0126 improvedthe apoptosis inducing ability of PCBL.Significance: In vitro findings suggest that PCBL works by initiating DNA damage and inducing apoptosis incancer cells and thus could be considered for further preclinical studies
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/11897
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