Cucurbitacin e Induces G 2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells

Wen Wen Huang, Jai Sing Yang, Meng Wei Lin, Po Yuan Chen, Shang Ming Chiou, Fu Shin Chueh, Yu Hsuan Lan, Shu Jen Pai, Minoru Tsuzuki, Wai Jane Ho, Jing Gung Chung

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (Δψ m) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured byWestern blotting. Our results demonstrated that cucurbitacin E-induced G 2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of Δψ m, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G 2/M phase arrest and apoptosis of T24 cells.

Original languageEnglish (US)
Article number952762
JournalEvidence-based Complementary and Alternative Medicine
Volume2012
DOIs
StatePublished - Feb 3 2012

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Cucurbitacins
STAT3 Transcription Factor
Urinary Bladder Neoplasms
Cell Division
Mitochondria
Apoptosis
Apoptotic Protease-Activating Factor 1
CDC2 Protein Kinase
Apoptosis Inducing Factor
Cyclin B
Triterpenes
Critical Pathways
Caspase 9
Caspase 8
Mitochondrial Membrane Potential
Annexin A5
Cell Cycle Checkpoints
Cytochromes c
Caspase 3
cucurbitacin E

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Cucurbitacin e Induces G 2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells. / Huang, Wen Wen; Yang, Jai Sing; Lin, Meng Wei; Chen, Po Yuan; Chiou, Shang Ming; Chueh, Fu Shin; Lan, Yu Hsuan; Pai, Shu Jen; Tsuzuki, Minoru; Ho, Wai Jane; Chung, Jing Gung.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2012, 952762, 03.02.2012.

Research output: Contribution to journalArticle

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author = "Huang, {Wen Wen} and Yang, {Jai Sing} and Lin, {Meng Wei} and Chen, {Po Yuan} and Chiou, {Shang Ming} and Chueh, {Fu Shin} and Lan, {Yu Hsuan} and Pai, {Shu Jen} and Minoru Tsuzuki and Ho, {Wai Jane} and Chung, {Jing Gung}",
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AU - Huang, Wen Wen

AU - Yang, Jai Sing

AU - Lin, Meng Wei

AU - Chen, Po Yuan

AU - Chiou, Shang Ming

AU - Chueh, Fu Shin

AU - Lan, Yu Hsuan

AU - Pai, Shu Jen

AU - Tsuzuki, Minoru

AU - Ho, Wai Jane

AU - Chung, Jing Gung

PY - 2012/2/3

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N2 - Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (Δψ m) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured byWestern blotting. Our results demonstrated that cucurbitacin E-induced G 2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of Δψ m, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G 2/M phase arrest and apoptosis of T24 cells.

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