Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer

Rachael R. Schulte; Amanda G. Linkous; Dennis E. Hallahan; Eugenia M. Yazlovitskaya

doi:10.1016/j.canlet.2011.02.015

Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer

Rachael R. Schulte, Amanda G. Linkous, Dennis E. Hallahan, Eugenia M. Yazlovitskaya

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA₂) inhibitor AACOCF₃ prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA₂ inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA₂ as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.

Original language	English
Pages (from-to)	137-143
Number of pages	7
Journal	Cancer Letters
Volume	304
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2011.02.015
State	Published - May 28 2011

Keywords

Cytosolic phospholipase A2
Lysophosphatidic acid
Lysophosphatidylcholine
Ovarian cancer
Radiation therapy

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10.1016/j.canlet.2011.02.015

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title = "Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer",

abstract = "In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3 prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA2 inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA2 as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.",

keywords = "Cytosolic phospholipase A2, Lysophosphatidic acid, Lysophosphatidylcholine, Ovarian cancer, Radiation therapy",

author = "Schulte, {Rachael R.} and Linkous, {Amanda G.} and Hallahan, {Dennis E.} and Yazlovitskaya, {Eugenia M.}",

note = "Funding Information: We would like to thank Ms. Allie Fu for help with animal studies. This work was supported by the Elizabeth H. and James S. McDonnell Distinguished Professorship and grants from the National Institutes of Health grants to D.E.H. (Washington, DC; R01-140220; R01-CA112385 and R01-CA88076) and to E.M.Y. from Elsa U. Pardee foundation (Midland, MI).",

year = "2011",

month = may,

day = "28",

doi = "10.1016/j.canlet.2011.02.015",

language = "English",

volume = "304",

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journal = "Cancer Letters",

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AU - Schulte, Rachael R.

AU - Linkous, Amanda G.

AU - Hallahan, Dennis E.

AU - Yazlovitskaya, Eugenia M.

N1 - Funding Information: We would like to thank Ms. Allie Fu for help with animal studies. This work was supported by the Elizabeth H. and James S. McDonnell Distinguished Professorship and grants from the National Institutes of Health grants to D.E.H. (Washington, DC; R01-140220; R01-CA112385 and R01-CA88076) and to E.M.Y. from Elsa U. Pardee foundation (Midland, MI).

PY - 2011/5/28

Y1 - 2011/5/28

N2 - In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3 prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA2 inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA2 as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.

AB - In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3 prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA2 inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA2 as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.

KW - Cytosolic phospholipase A2

KW - Lysophosphatidic acid

KW - Lysophosphatidylcholine

KW - Ovarian cancer

KW - Radiation therapy

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DO - 10.1016/j.canlet.2011.02.015

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AN - SCOPUS:79952735023

SN - 0304-3835

VL - 304

SP - 137

EP - 143

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer

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