Apoptotic mechanism of paclitaxel‐induced cell death in human head and neck tumor cell lines

Hsiao, Jenn-Ren; Leu, Sew Fen; Huang, Bu‐Miin

doi:10.1111/j.1600-0714.2008.00732.x

Cited by 54 publications

(31 citation statements)

References 31 publications

(46 reference statements)

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“…No general inhibitory trend was observed for the phosphorylation of Akt at serine residue 473, or of S6 ribosomal protein at serine residues 240/244, events indicative of PI3K pathway activation. Cell cycle analysis of HNSCC cell lines treated with rigosertib yielded results more representative of those expected from a cytotoxic drug, a complete G2 block in sensitive lines, than to those obtained with the PI3K targeting agent ZSTK474 (49). These studies confirm earlier observations indicating that multiple mechanisms are involved in the activity of rigosertib, including effects on signal transduction and mitotic pathways.…”

Section: Discussionmentioning

confidence: 84%

The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas

Anderson

Keysar

Bowles

et al. 2013

Molecular Cancer Therapeutics

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The dual pathway inhibitor rigosertib inhibits phosphoinositide 3-kinase (PI3K) pathway activation as well as polo-like kinase 1 (PLK1) activity across a broad spectrum of cancer cell lines. The importance of PIK3CA alterations in head and neck squamous cell cancer (HNSCC) has raised interest in exploring agents targeting PI3K, the product of PIK3CA. The genetic and molecular basis of rigosertib treatment response was investigated in a panel of 16 HNSCC cell lines, and direct patient tumor xenografts from 8 HNSCC patients (4 HPV16-positive). HNSCC cell lines and xenografts were characterized by pathway enrichment gene expression analysis, exon sequencing, gene copy number, western blotting, and IHC. Rigosertib had potent antiproliferative effects on 11 of the 16 HPV− HNSCC cell lines. Treatment sensitivity was confirmed in two cell lines using an orthotopic in vivo xenograft model. Growth reduction after rigosertib treatment was observed in 3/8 HNSCC direct patient tumor lines. The responsive tumor lines carried a combination of a PI3KCA activating event (amplification or mutation) and a p53 inactivating event (either HPV16-mediated or mutation-mediated TP53 inactivation). In this study, we evaluated the in vitro and in vivo efficacy of rigosertib in both HPV+ and HPV− HNSCCs focusing on inhibition of the PI3K pathway. Although consistent inhibition of the PI3K pathway was not evident in HNSCC, we identified a combination of PI3K/TP53 events necessary, but not sufficient for rigosertib-sensitivity.

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Section: Discussionmentioning

confidence: 84%

The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas

Anderson

Keysar

Bowles

et al. 2013

Molecular Cancer Therapeutics

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“…Among numerous antitumor drugs, the taxanes are widely recognized. Docetaxel, a derivative of taxane, is a highly effective antineoplastic drug applied to treatment of many malignant tumors, including lung cancer 1415. The existence of such antitumor drug alleviates the anxiety of clinical oncologists to a great extent.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of the M2 Isoform of Pyruvate Kinase (PKM2) with shRNA Enhances the Effect of Docetaxel in Human NSCLC Cell LinesIn Vitro

et al. 2016

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PurposeThe aim of our study was to explore the relationships between the M2 isoform of pyruvate kinase (PKM2) and the sensitivity of human non-small cell lung cancer (NSCLC) cells to docetaxel in vitro.Materials and MethodsWith the method of plasmid transfection, we silenced the expression of PKM2 successfully in A549 and H460 cells. Western blotting and real-time PCR were applied to detect PKM2 expression at protein and gene levels. Cell viability was examined by CCK8 assay. Cell cycle distribution and apoptosis were examined by flow cytometry. P21 and Bax were detected.ResultsExpression of PKM2 mRNA and protein were significantly decreased by shRNA targeting PKM2. Silencing of PKM2 increased docetaxel sensitivity of human NSCLC A549 and H460 cells in a collaborative manner, resulting in strong suppression of cell viability. The results of flow cytometric assays suggested that knockdown of PKM2 or docetaxel treatment, whether used singly or in combination, blocked the cells in the G2/M phase, which is in consistent with the effect of the two on the expression of p21. Cells with PKM2 silencing were more likely to be induced into apoptosis by docetaxel although knockdown of PKM2 alone can't induce apoptosis significantly, which is in consistent with the effect of the two on Bax expression.ConclusionThe results suggest that PKM2 knockdown could serve as a chemosensitizer to docetaxel in non-small lung cancer cells through targeting PKM2, leading to inhibition of cell viability, increase of cell arrest of G2/M phase and apoptosis.

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“…또한, 계속되는 적응증(류마티스성 관절염, 알츠하이 머 치료) 및 처방방법의 개발로 파클리탁셀 수요는 계속 늘어날 전 망이다 [2,3]. 파클리탁셀의 주요 생산 방법에는 주목나무(yew tree) 에서 직접 추출하는 방법, 주목나무에서 전구체를 얻어 반합성하는 방법, 주목나무에서 캘러스(callus)를 유도하여 식물세포를 배양하여 얻는 방법이 있다 [4][5][6].…”

Section: 서 론unclassified

Ultrasound-Assisted Liquid-Liquid Extraction for Recovery of Paclitaxel from Plant Cell Cultures

Ha¹,

Kim²

2016

Korean Chemical Engineering Research

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− In this study, an efficient ultrasound-assisted liquid-liquid extraction process was developed for recovering of paclitaxel from plant cell cultures. The optimal ultrasonic power and operating time were 250 W and 15 min at fixed ratio of bottom phase, methylene chloride to top phase, MeOH (25%, v/v). Under the optimal conditions developed in the present method, most of the paclitaxel (~92%) was recovered from crude extract by a single extraction step. Due to the synergistic effect of ultrasound by the addition of inorganic salt, an appropriate inorganic salt concentration and the ultrasonic power were found to be required for the effective recovery of paclitaxel using ultrasound-assisted liquid-liquid extraction.

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Apoptotic mechanism of paclitaxel‐induced cell death in human head and neck tumor cell lines

Abstract: Paclitaxel activated cell cycle arrest and caspase protein expressions to induce apoptosis in HNSCC cell lines.

Cited by 54 publications

References 31 publications

The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas

The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas

Knockdown of the M2 Isoform of Pyruvate Kinase (PKM2) with shRNA Enhances the Effect of Docetaxel in Human NSCLC Cell LinesIn Vitro

Ultrasound-Assisted Liquid-Liquid Extraction for Recovery of Paclitaxel from Plant Cell Cultures

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