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P53-independent Apoptosis Induced By Paclitaxel Through An Indirect Mechanism.

J. Lanni, S. Lowe, E. Licitra, J. Liu, T. Jacks
Published 1997 · Biology, Medicine

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The efficacy of chemotherapeutic agents may be determined by a number of different factors, including the genotype of the tumor cell. The p53 tumor suppressor gene frequently is mutated in human tumors, and this may contribute to chemotherapeutic resistance. We tested the requirement for wild-type p53 in the response of tumor cells to treatment with paclitaxel (trade name Taxol), an antineoplastic agent that stabilizes cellular microtubules. Although paclitaxel is broadly effective against human tumor xenografts in mice, including some known to carry p53 mutations, we found that p53-containing mouse tumor cells were significantly more sensitive to direct treatment with this drug than were p53-deficient tumor cells. In an attempt to reconcile this apparent discrepancy, we examined the requirement for p53 in the cytotoxic effects of tumor necrosis factor alpha (TNF-alpha), a cytokine released from murine macrophages upon paclitaxel treatment. Conditioned medium from paclitaxel-treated macrophages was capable of inducing p53-independent apoptosis when applied to transformed mouse embryonic fibroblasts and was inhibitable by antibodies against TNF-alpha. Furthermore, in response to direct treatment with TNF-alpha, both wild-type and p53-deficient tumor cells underwent apoptosis to similar extents and with similar kinetics. Our results suggest that the efficacy of paclitaxel in vivo may be due not only to its microtubule-stabilizing activity, but its ability to activate local release of an apoptosis-inducing cytokine.
This paper references
Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.
M. Wani (1971)
Promotion of microtubule assembly in vitro by taxol
P. Schiff (1979)
Taxol stabilizes microtubules in mouse fibroblast cells.
P. Schiff (1980)
Antineoplastic activity of two taxol derivatives on an ovarian tumor xenografted into nude mice.
J. Riondel (1988)
Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas.
S. Baker (1989)
Shared actions of endotoxin and taxol on TNF receptors and TNF release.
A. Ding (1990)
Antiproliferative and cytotoxic effects of single and combined treatment with tumor necrosis factor alpha and/or alpha interferon on a human renal cell carcinoma xenotransplanted into nu/nu mice: cell kinetic studies.
H. Baisch (1990)
Mechanism of inhibition of cell proliferation by Vinca alkaloids.
M. Jordan (1991)
Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors.
A. Asher (1991)
Taxol, a microtubule‐stabilizing antineoplastic agent, induces expression of tumor necrosis factor α and interleukin‐1 in macrophages
C. Bogdan (1992)
Genetic aspects of multidrug resistance
J. L. Biedler (1992)
Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines.
M. Reiss (1992)
Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages.
C. Manthey (1992)
The origin and function of tumor-associated macrophages.
A. Mantovani (1992)
Tumor Necrosis Factors: Their Emerging Role in Medicine, ed
D. Spriggs (1992)
Thymocyte apoptosis induced by p53-dependent and independent pathways
A. Clarke (1993)
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
J. Harper (1993)
Antitumor activity of taxol (NSC-125973) in human ovarian carcinomas growing in the peritoneal cavity of nude mice.
M. I. Nicoletti (1993)
WAF1, a potential mediator of p53 tumor suppression
W. El-Deiry (1993)
Taxol enhances but does not induce interleukin-1 beta and tumor necrosis factor-alpha production.
J. Allen (1993)
Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.
M. Jordan (1993)
Lipopolysaccharide antagonists block taxol-induced signaling in murine macrophages
C. Manthey (1993)
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
S. Lowe (1993)
Taxol shares the ability of bacterial lipopolysaccharide to induce tyrosine phosphorylation of microtubule-associated protein kinase.
A. Ding (1993)
p53 is required for radiation-induced apoptosis in mouse thymocytes
S. Lowe (1993)
p53 status and the efficacy of cancer therapy in vivo.
S. Lowe (1994)
Molecular mechanisms of tumor necrosis factor‐induced cytotoxicity
R. Beyaert (1994)
Tumor spectrum analysis in p53-mutant mice
T. Jacks (1994)
Relationship between the structure of taxol and other taxanes on induction of tumor necrosis factor-alpha gene expression and cytotoxicity.
C. Burkhart (1994)
Tumor necrosis factor for the treatment of malignancies.
U. Hieber (1994)
Rationale for using TNFα and chemotherapy in regional therapy of melanoma
F. Lejeune (1994)
Sequence‐dependent antitumor activity of paclitaxel (taxol) and cisplatin in vivo
C. Milross (1995)
p53 point mutation and survival in colorectal cancer patients.
H. Goh (1995)
A p53-dependent mouse spindle checkpoint
S. Cross (1995)
Combination of immunotherapy with cyclophosphamide/actinomycin D chemotherapy potentiates antileukemic effect and reduces toxicity in a L1210 leukemia model in mice.
W. Lasek (1995)
Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice.
F. Innocenti (1995)
Drug therapy : paclitaxel (Taxol)
E. Rowinsky (1995)
Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.
V. Rusch (1995)
Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance.
John Calvin Reed (1995)
Cancer therapy and p53.
S. Lowe (1995)
Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy
J. Bergh (1995)
Tumor suppressor p53 mutations and breast cancer: a critical analysis.
M. Ozbun (1995)
Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents.
D. Hawkins (1996)
Transducers of life and death: TNF receptor superfamily and associated proteins.
S. Baker (1996)
p53 and chemosensitivity
G. Wu (1996)
Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients
T. Aas (1996)
Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis
A. Wahl (1996)
Augmentation of antitumor efficacy by the combination of actinomycin D with tumor necrosis factor-alpha and interferon-gamma on a melanoma model in mice.
W. Lasek (1996)
Lanni et al
T. Jacks (1997)

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B. Ai (2016)
Are pharmacogenomic biomarkers an effective tool to predict taxane toxicity and outcome in breast cancer patients? Literature review
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C. Lima (2015)
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R. Altıntaş (2015)
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Fan An (2015)
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