Para-amino benzoic acid (PABA), a radiation and chemotherapy sensitizer

Abstract

PABA or para-amino benzoic acid is a water-soluble compound that is widely available as a dietary supplement and has been used as a component of sunscreens. PABA has also been tested in clinical trials to evaluate the effects in the treatment of scleroderma and Peyronies disease. Although these trials did not demonstrate improvement, PABA was well tolerated and administered with ease. Previously, we demonstrated that PABA enhances the effects of docetaxel in the 4T1 syngeneic murine model of mammary carcinoma (AACR-NCI-EORTC, Nov. 2003). We also demonstrated that PABA enhances the effects of radiation in the 4T1 syngeneic murine model (AACR Radiation Biology and Cancer Research, Feb. 2004). We now seek to examine the effects of trimodality therapy with the combination of radiation, docetaxel, and PABA in the 4T1 murine model. 4T1 tumor cells (5 x 104) were injected subcutaneously into the flank of eight groups of five BALB/C mice. Three days later, mice were randomly assigned to receive PABA (1 mg/day). A second randomization was performed to docetaxel, 4 mg/kg on days 7, 14, 21, 28, and 35. At 14 days post-implantation, a third randomization to radiation treatment (RT) was performed. A 60Co source was used to deliver two fractions of 5 Gy to the tumors. Tumors were measured and volumes were calculated weekly, for 37 days ((L2xW)/2). For each group of treated animals, tumor inhibition was reported as the ratio of the average volume compared to that of controls. Results were also compared between groups. P values were determined using Student’s T-test. At day 37, PABA treatment had minimal effect on tumor growth (P = 0.47); PABA, docetaxel, and radiation therapy inhibited growth by 50% as compared to controls (P = 0.01); PABA, docetaxel, and radiation therapy inhibited growth by 31% as compared to PABA and RT (P = 0.03); PABA, docetaxel, and radiation therapy inhibited growth by 48% as compared to PABA and docetaxel (P = 0.02). Mean tumor volumes and comparisons between groups are displayed in table 1. Significant differences were seen in comparisons of tumor volumes between groups 5, 6, and 7. We have previously demonstrated that PABA enhances the effects of both radiation and docetaxel in the 4T1 syngeneic murine mammary model. Here, we conclude that the trimodality approach of PABA, radiation therapy, and docetaxel further inhibits tumor growth. Due to the tolerability and ease of administration of PABA, these findings have high translational potential.