Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel

Autoren

Steve B Jiang
John Wolfgang
Gig S Mageras

DOI

10.1016/j.ijrobp.2007.07.2386

ISSN

0360-3016

Ausgabe der Veröffentlichung

1

Zeitschrift

International Journal of Radiation Oncology*Biology*Physics

Sprache

en

Paginierung

S103 - S107

Datum der Veröffentlichung

2008

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.ijrobp.2007.07.2386

Datum der Datenerfassung

2018

Titel

Quality Assurance Challenges for Motion-Adaptive Radiation Therapy: Gating, Breath Holding, and Four-Dimensional Computed Tomography

Ausgabe der Zeitschrift

71

Data source: Crossref

Abstract

Paclitaxel, a natural product originally isolated from Taxus brevifolia, belongs to the most successful anticancer drugs. Nevertheless, its poor water solubility represents a considerable disadvantage in clinical use, and novel derivatives with improved pharmacological features are required. We isolated 7-xylosyl-10-deacetylpaclitaxel from Taxus chinensis, which reveals higher water solubility than paclitaxel. This compound induced mitotic cell cycle arrest and apoptosis as measured by flow cytometry, DNA laddering, and transmission electron microscopy. Pro-apoptotic Bax and Bad protein expression was up-regulated and anti-apoptotic Bcl-2 and Bcl-XL expression down-regulated, which lead to a disturbance of the mitochondrial membrane permeability and to the activation of caspase-9. In turn, caspase-9 activated downstream caspases-3 and -6, but not caspase-8. Bid was also activated by caspase-3. Reversely, treatment with a caspase-10-specific inhibitor could not protect PC-3 cells from 7-xylosyl-10-deacetyl-paclitaxel-triggered apoptosis. Moreover, 7-xylosyl-10-deacetylpaclitaxel had no effect on the expression of CD95 and NF-kappaB proteins, indicating that apoptosis was induced through the mitochondrial-dependent pathway in PC-3 cells.

Addresses

Key Laboratory of Foresty Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, P.R. China.

Autoren

Shougang Jiang
Yuangang Zu
Yuejie Fu
Yu Zhang
Thomas Efferth

DOI

10.1016/j.ijrobp.2007.07.2386

eISSN

1791-2423

Externe Identifier

PubMed Identifier: 18575755

Open access

false

ISSN

1019-6439

Ausgabe der Veröffentlichung

1

Zeitschrift

International journal of oncology

Schlüsselwörter

Cell Line, Tumor
Mitochondria
Humans
Taxus
Prostatic Neoplasms
Paclitaxel
Annexin A5
NF-kappa B
Antineoplastic Agents, Phytogenic
Cell Cycle
Apoptosis
DNA Fragmentation
Cell Proliferation
Male
bcl-X Protein
BH3 Interacting Domain Death Agonist Protein
Caspase 10
fas Receptor

Sprache

eng

Medium

Print

Paginierung

103 - 111

Datum der Veröffentlichung

2008

Status

Published

Datum der Datenerfassung

2008

Titel

Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

33

Data source: Europe PubMed Central

Abstract

Paclitaxel, a natural product originally isolated from Taxus brevifolia, belongs to the most successful anticancer drugs. Nevertheless, its poor water solubility represents a considerable disadvantage in clinical use, and novel derivatives with improved pharmacological features are required. We isolated 7-xylosyl-10-deacetylpaclitaxel from Taxus chinensis, which reveals higher water solubility than paclitaxel. This compound induced mitotic cell cycle arrest and apoptosis as measured by flow cytometry, DNA laddering, and transmission electron microscopy. Pro-apoptotic Bax and Bad protein expression was up-regulated and anti-apoptotic Bcl-2 and Bcl-XL expression down-regulated, which lead to a disturbance of the mitochondrial membrane permeability and to the activation of caspase-9. In turn, caspase-9 activated downstream caspases-3 and -6, but not caspase-8. Bid was also activated by caspase-3. Reversely, treatment with a caspase-10-specific inhibitor could not protect PC-3 cells from 7-xylosyl-10-deacetyl-paclitaxel-triggered apoptosis. Moreover, 7-xylosyl-10-deacetylpaclitaxel had no effect on the expression of CD95 and NF-kappaB proteins, indicating that apoptosis was induced through the mitochondrial-dependent pathway in PC-3 cells.

Autoren

Shougang Jiang
Yuangang Zu
Yuejie Fu
Yu Zhang
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/18575755

ISSN

1019-6439

Ausgabe der Veröffentlichung

1

Zeitschrift

Int J Oncol

Schlüsselwörter

Annexin A5
Antineoplastic Agents, Phytogenic
Apoptosis
BH3 Interacting Domain Death Agonist Protein
Caspase 10
Cell Cycle
Cell Line, Tumor
Cell Proliferation
DNA Fragmentation
Humans
Male
Mitochondria
NF-kappa B
Paclitaxel
Prostatic Neoplasms
Taxus
bcl-X Protein
fas Receptor

Sprache

eng

Country

Greece

Paginierung

103 - 111

Datum der Veröffentlichung

2008

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2008

Titel

Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

33

Data source: PubMed

Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel

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