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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