INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin.

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.

• Authors: Kathryn A Mason, David Valdecanas, Nancy R Hunter, Luka Milas
• Journal: Investigational new drugs (Invest New Drugs) Vol. 26 Issue 1 Pg. 1-5 (Feb 2008) ISSN: 0167-6997 [Print] United States
• PMID: 17628743 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• INO 1001
• Indoles
• Poly(ADP-ribose) Polymerase Inhibitors
• Tumor Suppressor Protein p53
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Breast Neoplasms (metabolism, pathology, prevention & control)
• Cell Line, Tumor
• Doxorubicin (pharmacology, therapeutic use)
• Drug Synergism
• Drug Therapy, Combination
• Humans
• Indoles (pharmacology, therapeutic use)
• Mammary Neoplasms, Experimental (metabolism, pathology, prevention & control)
• Mice
• Mice, Inbred C3H
• Mice, Nude
• Poly(ADP-ribose) Polymerase Inhibitors
• Tumor Burden (drug effects)
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays