Chemopreventive Effects of Propolis in the MNU-Induced Rat Mammary Tumor Model

Currently, one of the central problems in cancer management is the relapse of disease following conventional treatments, yet few therapeutic agents targeting resistance and tolerance exist. Propolis is known as a healing agent since ancient times. Therefore, over time, its curative properties have kept the interest of scientists, thus leading permanently to investigations of its other possible undiscovered effects. In this context, current experiments were performed to establish the chemopreventive potential of propolis extract (PE) (1.05 mg/kg BW/day) in N-methyl-N-nitrosourea- (MNU-) induced rat mammary tumors. MNU-inoculated/PE-treated rats had tumors of different physical attributes compared with control rats MNU-inoculated. The number of developed tumors (mean 49% versus 100%), incidence (mean 49% versus 100%), multiplicity (1.8 versus 3.7 (p<0.001)), tumor volume (mean 10 cm3 versus 16 cm3 (p<0.001)), and weight of the tumor mass (mean 7.42 g versus 9.00 g (p<0.05)) were noted. The numbers of grade I tumors recorded for MNU-inoculated rats were 24 (Group 1) and 7 (Group 2) for MNU-induced/PE-treated rats. In the serum of rats MNU-inoculated/PE-treated were found higher levels of antioxidative enzymes (SOD, CAT, and GPx) than in MNU-induced. Taken together, these data indicate that propolis could be a chemopreventive agent against MNU-induced mammary carcinogenesis.

Arachidonic acid enhances TNF-α-induced tumorigenesis in human breast cancer cell line and rat mammary tumors.

Background: Our group has previously reported that arachidonic acid (AA, 20:4n-6) levels are 10 times higher in rat mammary tumor tissue compared to the normal mammary gland. Nuclear factor kappaB (NF-κB) activation is often found to be constitutive in human breast cancer, showing higher activation in the more aggressive subtypes. Methods : We incubated the human breast cancer MCF-7 cells for 48 h, in medium supplemented with BSA or BSA-bound 10, 50 and 100 mM AA, then added the same medium alone or supplemented with 10 ng/mL TNF-α. Thirty carcinogen-induced rat mammary tumors, weighting between 0.3 g and 19.2 g, were examined. Results : The carcinogen-induced rat mammary tumor weight was positively correlated with AA level, p-Akt/Akt ratio, nuclear p65, c-Myc and VEGF expression. In MCF-7 cells, AA alone had no effect on NF-kB activation. However, 50 or 100 μM AA pretreatment enhanced TNF-α-induced p-Akt/Akt, and p-IkB expression, with subsequent decrease in IkB. Thereafter, an increase in nuclear p65, nuclear c-Myc expression, NF-kB gene reporter activity and cell proliferation was observed. Conclusion : AA can effectively augment p-Akt signaling and TNF-α-induced NF-kB activation to promote the tumorigenesis in breast cancer. Our study indicates that AA may influence tumor progression by increasing the aggressiveness of breast cancer.