Kavindra Nath1, David Nelson1, Dennis Leeper2, and Jerry Glickson1
1University of Pennsylvania, Philadelphia, PA, United States, 2Thomas Jefferson University, Philadelphia, PA, United States
Lonidamine
(LND) effects were measured in vivo by
31P and 1H MRS in androgen-independent (PC3) and androgen-dependent
(LNCaP) prostate cancer xenografts indicating a sustained and tumor-selective
decrease in intracellular pH (pHi) and extracellular pH (pHe), and decrease in tumor
bioenergetics (βNTP/Pi) by 75.0 % and 79.0 % in PC3 and LNCaP, respectively,
relative to the baseline levels. Steady-state levels of tumor lactate were
significantly increased ~ 2 fold at 60 min. post-LND. The decline of pHi, pHe, bioenergetics
and increase in lactate produced increased therapeutic efficacy when LND was combined
with other therapeutic interventions (chemotherapy, radiation, and hyperthermia).