INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase,enhances tumor response to doxorubicin |
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Authors: | Kathryn A Mason David Valdecanas Nancy R Hunter Luka Milas |
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Institution: | (1) Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA |
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Abstract: | Summary 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. |
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Keywords: | Poly(ADP-ribose) INO-1001 Doxorubicin p53-Deficient cancer cells Doxorubicin-induced apoptosis |
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