Taxol induces caspase-10-dependent apoptosis

Soo Jung Park, Ching Haung Wu, John D. Gordon, Xiaoling Zhong, Armaghan Emami, Ahmad R. Safa

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Taxol (paclitaxel) is known to inhibit cell growth and trigger significant apoptosis in various cancer cells. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. In this study we investigated death receptors, FAS-associated death domain protein (FADD), the activation of caspases-10 and -8 as well as the downstream caspases, and reactive oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line. Pretreating the cells with neutralizing antibodies to Fas, tumor necrosis factor (TNF)-α receptor 1, or TNF-related apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced apoptosis, but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD. Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, despite the release of cytochrome c from the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was also associated with decreased mitochondrial membrane potential (ΔΨm) and a significant increase in ROS generation. However, increased ROS production was not directly involved in taxol-triggered apoptosis. Therefore, these results demonstrate for the first time that taxol induces FADD-dependent apoptosis primarily through activation of caspase-10 but independently of death receptors.

Original languageEnglish (US)
Pages (from-to)51057-51067
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number49
DOIs
StatePublished - Dec 3 2004

Fingerprint

Caspase 10
Paclitaxel
Apoptosis
Death Domain Receptors
Caspase 8
Cells
TNF-Related Apoptosis-Inducing Ligand Receptors
Reactive Oxygen Species
Chemical activation
Proteins
CASP8 and FADD-Like Apoptosis Regulating Protein
Lamin Type B
Caspase 6
X-Linked Inhibitor of Apoptosis Protein
Inhibitor of Apoptosis Proteins
Mitochondria
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
Caspase 9
Mitochondrial Membrane Potential

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, S. J., Wu, C. H., Gordon, J. D., Zhong, X., Emami, A., & Safa, A. R. (2004). Taxol induces caspase-10-dependent apoptosis. Journal of Biological Chemistry, 279(49), 51057-51067. https://doi.org/10.1074/jbc.M406543200

Taxol induces caspase-10-dependent apoptosis. / Park, Soo Jung; Wu, Ching Haung; Gordon, John D.; Zhong, Xiaoling; Emami, Armaghan; Safa, Ahmad R.

In: Journal of Biological Chemistry, Vol. 279, No. 49, 03.12.2004, p. 51057-51067.

Research output: Contribution to journalArticle

Park, SJ, Wu, CH, Gordon, JD, Zhong, X, Emami, A & Safa, AR 2004, 'Taxol induces caspase-10-dependent apoptosis', Journal of Biological Chemistry, vol. 279, no. 49, pp. 51057-51067. https://doi.org/10.1074/jbc.M406543200
Park, Soo Jung ; Wu, Ching Haung ; Gordon, John D. ; Zhong, Xiaoling ; Emami, Armaghan ; Safa, Ahmad R. / Taxol induces caspase-10-dependent apoptosis. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 49. pp. 51057-51067.
@article{998456e6b4044f61ac21e4095dc623ea,
title = "Taxol induces caspase-10-dependent apoptosis",
abstract = "Taxol (paclitaxel) is known to inhibit cell growth and trigger significant apoptosis in various cancer cells. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. In this study we investigated death receptors, FAS-associated death domain protein (FADD), the activation of caspases-10 and -8 as well as the downstream caspases, and reactive oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line. Pretreating the cells with neutralizing antibodies to Fas, tumor necrosis factor (TNF)-α receptor 1, or TNF-related apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced apoptosis, but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD. Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, despite the release of cytochrome c from the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was also associated with decreased mitochondrial membrane potential (ΔΨm) and a significant increase in ROS generation. However, increased ROS production was not directly involved in taxol-triggered apoptosis. Therefore, these results demonstrate for the first time that taxol induces FADD-dependent apoptosis primarily through activation of caspase-10 but independently of death receptors.",
author = "Park, {Soo Jung} and Wu, {Ching Haung} and Gordon, {John D.} and Xiaoling Zhong and Armaghan Emami and Safa, {Ahmad R.}",
year = "2004",
month = "12",
day = "3",
doi = "10.1074/jbc.M406543200",
language = "English (US)",
volume = "279",
pages = "51057--51067",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "49",

}

TY - JOUR

T1 - Taxol induces caspase-10-dependent apoptosis

AU - Park, Soo Jung

AU - Wu, Ching Haung

AU - Gordon, John D.

AU - Zhong, Xiaoling

AU - Emami, Armaghan

AU - Safa, Ahmad R.

PY - 2004/12/3

Y1 - 2004/12/3

N2 - Taxol (paclitaxel) is known to inhibit cell growth and trigger significant apoptosis in various cancer cells. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. In this study we investigated death receptors, FAS-associated death domain protein (FADD), the activation of caspases-10 and -8 as well as the downstream caspases, and reactive oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line. Pretreating the cells with neutralizing antibodies to Fas, tumor necrosis factor (TNF)-α receptor 1, or TNF-related apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced apoptosis, but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD. Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, despite the release of cytochrome c from the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was also associated with decreased mitochondrial membrane potential (ΔΨm) and a significant increase in ROS generation. However, increased ROS production was not directly involved in taxol-triggered apoptosis. Therefore, these results demonstrate for the first time that taxol induces FADD-dependent apoptosis primarily through activation of caspase-10 but independently of death receptors.

AB - Taxol (paclitaxel) is known to inhibit cell growth and trigger significant apoptosis in various cancer cells. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. In this study we investigated death receptors, FAS-associated death domain protein (FADD), the activation of caspases-10 and -8 as well as the downstream caspases, and reactive oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line. Pretreating the cells with neutralizing antibodies to Fas, tumor necrosis factor (TNF)-α receptor 1, or TNF-related apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced apoptosis, but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD. Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, despite the release of cytochrome c from the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was also associated with decreased mitochondrial membrane potential (ΔΨm) and a significant increase in ROS generation. However, increased ROS production was not directly involved in taxol-triggered apoptosis. Therefore, these results demonstrate for the first time that taxol induces FADD-dependent apoptosis primarily through activation of caspase-10 but independently of death receptors.

UR - http://www.scopus.com/inward/record.url?scp=10944257440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10944257440&partnerID=8YFLogxK

U2 - 10.1074/jbc.M406543200

DO - 10.1074/jbc.M406543200

M3 - Article

C2 - 15452117

AN - SCOPUS:10944257440

VL - 279

SP - 51057

EP - 51067

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 49

ER -