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Abstract #1140

Lonidamine sensitizes human breast cancer xenografts to Doxorubicin via metabolic modulations

Kavindra Nath 1 , Jerry D Glickson 1 , David S Nelson 1 , Daniel F Heitjan 1 , Dennis B Leeper 2 , I-Wei Chen 1 , and Rong Zhou 1

1 University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2 Thomas Jefferson University, Philadelphia, Pennsylvania, United States

We demonstrate that a small molecule, lonidamine (LND), sensitizes breast cancers to the chemotherapeutic drug, Doxorubicin, via selective intracellular acidification and suppression of high energy phosphate production of the tumor. In vivo MR spectroscopy of human breast cancer xenografts show that LND treatment induces a maximal decrease of intracellular pH of 0.54 unit and depletion of NTP/Pi by 77% accompanied by 3-fold increase of tumor lactate content. One treatment with LND (100 mg/kg, i.p.) combined with one injection of doxorubicin (12 mg/kg, i.v.) leads to a tumor growth delay of 23 days and log10 cell-kill of 1.70. These results suggest that LND potentiates chemotherapeutics by modulating cancer metabolism.

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