Destruxin B, a cyclic depsipeptide, is a secondary metabolite isolated from the fungus Metarhizium anisopliae. Each of the mycotoxins, destruxin A, B, and E, were individually found to display antitumor effects on leukemic cells in vitro. In addition, each destruxin was found to produce antiproliferative effects in colon cancer cells and to inhibit the migration and tube formation of human endothelial cells. Although the inhibition of vacuolar-type ATPase by destruxin B has been found to be weaker than bafilomycin A1, inhibition by destruxin B was found to be readily reversible, which makes it more useful as a probe of V-ATPase function. In human colorectal cancer cells destruxin B treatment resulted in suppressed proliferation and induced cell cycle arrest. Administration of destruxin B to human non-Hodgkin lumphoma cells resulted in apoptosis induced by attenuation of the mitochondrial membrane potential.