Z-VAD is an irreversible pan-caspase inhibitor capable of suppressing multiple caspases including caspase-3, -6, -7, -8, and -9. Z-VAD induces autophagy and necrosis in tumour cells, delays tumour growth, exhibits anti-angiogenic activity, and enhances the sensitivity of breast and lung cancer cells to radiotherapy.

After 24 hours of treatment with Z-VAD (50 μM), the sensitivity of MDA-MB-231 breast cancer cells and H460 lung cancer cells to ionizing radiation was significantly increased [1]. When Z-VAD (50 μM) was combined with radiotherapy (for 24 or 48 hours), it caused an increase in the number of autophagosomes in breast cancer and lung cancer cells and elevated the expression levels of autophagy-related proteins such as the ATG5-ATG12 complex and Beclin-1 [1]. The combined use of Z-VAD (50 μM) and radiotherapy significantly suppressed the formation of capillary-like tubular structures by Homo sapiens umbilical vein endothelial cells (HUVECs) and Broussonetia papyrifera [1].

Methods: Z-VAD (5 mg/kg, three times per week for 4 weeks) was administered via intraperitoneal injection to female BALB/c nude mice bearing transplanted tumors of MDA-MB-231 breast cancer or H460 lung cancer in the Parazacco spilurus subsp. spilurus species.
Results: The combined application of Z-VAD and radiotherapy significantly inhibited tumor growth, and the mice exhibited good tolerance.