Caffeic Acid Phenethyl Ester (CAPE) Inhibits Growth of Chromosomally instable bub1Δ mutant in Saccharomyces cerevisiae

Abstract

Chromosomal instability (CIN) is a hallmark of cancer cells. Spindle Assembly Checkpoint (SAC) proteins such as Bub1 monitor errors in chromosome segregation and cause cell cycle delay to prevent CIN. Altered expression of BUBl is observed in several tumor samples and cancer cell lines which display CIN. Caffeic Acid Phenethyl Ester (CAPE) which is an active component of propolis obtained from bee hives has anti-inflammatory antioxidant and anticarcinogenic properties. We used budding yeast S. cerevisiae as a model organism to investigate the molecular mechanism by which CAPE can inhibit the growth of cells with high levels of CIN. Here we show that CAPE leads to growth inhibition of bub1{Delta} strains. CAPE treatment suppressed chromosome mis-segregation in bub1{Delta} strain possibly due to apoptosis of chromosomally instable bub1{Delta} cells. We propose that CAPE may serve as a potential therapeutic agent for treatment of BUB1 deficient cancers and other cancers that exhibit CIN.