Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice

This French pharmacology group had previously shown fisetin can stabilise the internal skeleton of blood vessel lining cells. Here they tested whether that translates into blocking tumour blood vessel growth (angiogenesis) and slowing a lung cancer in living mice, and whether pairing fisetin with a low, non-toxic dose of the chemotherapy drug cyclophosphamide could do even better.

Fisetin killed lung cancer cells and endothelial cells in the dish at similar concentrations, and at lower, non-toxic doses it blocked endothelial cell migration and their ability to form capillary-like networks. In mice, fisetin alone shrank Matrigel-plug blood vessel formation and produced a 67% reduction in lung tumour growth - matching the 66% reduction from low-dose cyclophosphamide alone.

The headline finding is the combination: fisetin plus low-dose cyclophosphamide together produced a 92% reduction in tumour growth, with tumour blood vessel density falling to almost nothing on biopsy, while body weight loss stayed modest (around 4-5%), suggesting the combination was well tolerated in the mice.

As with other fisetin cancer papers in this Data Center, the effective doses here were high-dose intraperitoneal injections in a mouse cancer model, not oral fisetin supplementation, so this supports a laboratory antiangiogenic mechanism rather than a proven benefit for cancer patients taking oral fisetin.