5-Aminolevulinic Acid Triggered by Ultrasound Halts Tumor Proliferation in a Syngeneic Model of Breast Cancer

Sonodynamic therapy is a bimodal therapeutic approach in which a chemical compound and ultrasound (US) synergistically act to elicit oxidative damage, triggering cancer cell death. Despite encouraging results, mainly for anticancer treatment, sonodynamics is still far from having a clinical application. Therefore, to close the gap between the bench and bedside, more in vivo studies are needed. In this investigation, the combined effect of 5-aminolevulinic acid (Ala), a natural porphyrin precursor, plus exposure to US, was investigated in vivo on a syngeneic breast cancer model. Real-time RT-PCR, Western blotting, and immunohistochemistry assays were performed to evaluate the effect of sonodynamic treatment on the main cancer hallmarks. The sonodynamic-treated group had a significant reduction (p ≤ 0.0001) in tumor size compared to the untreated group, and the Ala- and US-only treated groups, where a strong decrease (p ≤ 0.0001) in Ki67 protein expression was the most relevant feature of sonodynamic-treated cancer tissues. Moreover, oxidative stress was confirmed as the pivotal driver of the anticancer effect through cell cycle arrest, apoptosis, and autophagy; thus, sonodynamics should be explored further for cancer treatment.