Abstract
Poly(ADP-ribose) synthetase inhibitor, INO-1001, is known to sensitize cells to radiation in vitro by inhibiting the repair of DNA damage. Recent evidence has suggested that PARP inhibition may also be a way of selectively targeting p53 deficient cancer cells. The present study tested INO-1001 for its in vivo effect on the chemoresponse of two p53 deficient tumors, human breast cancer MDA-MB-231 and murine mammary carcinoma MCa-K. Doxorubicin was used as the DNA damaging agent and tumor growth delay assay was used as the endpoint. Results showed that INO-1001 was highly effective in enhancing the anti-tumor effects of Doxorubicin for both MDA-MB-231 (EF=1.88) and MCa-K (EF=1.64). We conclude that PARP inhibitor INO-1001 has high potential for enhancing the anti-tumor effects of chemotherapy agents such as Doxorubicin against p53 deficient breast cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibiotics, Antineoplastic / pharmacology
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Antibiotics, Antineoplastic / therapeutic use
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Breast Neoplasms / prevention & control
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Cell Line, Tumor
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Doxorubicin / pharmacology*
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Doxorubicin / therapeutic use
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Drug Synergism
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Drug Therapy, Combination
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Humans
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Indoles / pharmacology*
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Indoles / therapeutic use
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Mammary Neoplasms, Experimental / metabolism
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / prevention & control*
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Mice
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Mice, Inbred C3H
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Mice, Nude
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Poly(ADP-ribose) Polymerase Inhibitors*
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Tumor Burden / drug effects
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Tumor Suppressor Protein p53 / metabolism
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Xenograft Model Antitumor Assays*
Substances
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Antibiotics, Antineoplastic
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INO 1001
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Indoles
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Poly(ADP-ribose) Polymerase Inhibitors
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Tumor Suppressor Protein p53
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Doxorubicin