A new study has reported that propranolol (Inderal) can strengthen the anti-tumor efficacy of Taxol (paclitaxel) and 5-FU (5-fluorouracil) chemotherapy. Propranolol is a beta blocker used to treat high blood pressure and other heart conditions. Recent studies have reported that the use of beta blockers such as propranolol before diagnosis or during treatment could increase the relapse-free survival and overall survival of breast cancer patients. The authors therefore hypothesized that propranolol may be able to heighten the efficacy of chemotherapy either by means of direct effects on cancer cells or through anti-angiogenic mechanisms. The authors used cell and animal studies to examine this question.
Cell studies demonstrated that propranolol induced dose-dependent anti-proliferative effects in nine human cancer and normal cell lines. Propranolol reduced angiogenesis (new blood vessel formation) at non-toxic concentrations. Combining Taxol or 5-FU with propranolol at the lowest effective concentrations resulted in either synergistic, additive or antagonistic effects on cell proliferation depending on cell type and dose of chemotherapy used. Breast cancer cells were among the most responsive to the propranolol-chemotherapy drug combinations. In addition, low concentrations of propranolol enhanced the anti-angiogenic effects of Taxol and 5-FU.
To conduct the animal studies, the authors generated tumors in mice by injecting MDA-MB-231 triple negative human breast cancer cells into their mammary fat pads. When used alone, propranolol induced only transient, if any, anti-tumor effects, and did not increase the survival time of the mice. However, when propranolol was combined with Taxol or 5-FU, a more profound and sustained anti-tumor effect was observed. Combining Taxol with propranolol increased the median survival of the mice by 79% compared to the survival benefit induced by taxol alone. The improvement in survival benefit induced by propranolol plus 5-FU was 19%. The authors conclude that propranolol can increase the anti-angiogenic effects and anti-tumor efficacy of chemotherapy. The current results, together with previous retrospective clinical data, suggest that use of propranolol concurrently with chemotherapy may improve the outcome of breast cancer patients.