The use of
doxorubicin (Dox) was severely constrained by dose-dependent side effects, which might be attenuated by combining a "sensitizer" to decrease its cumulative dosage. In this study, it was investigated whether
ocotillol could enhance the antiproliferation activity of Dox. MTT assays and xenograft
tumor model were firstly conducted to evaluate the effect of
ocotillol on the antitumor activity of Dox. Flow cytometry and Hoechst staining assays were then performed to assess cell apoptosis. Western blot and real-time PCR were finally used to detect the expression of p53 and its target genes. Our results showed
ocotillol to enhance Dox-induced cell death in p53 wild-type
cancer cells. Compared with Dox alone, Dox with
ocotillol (Dox-O) could induce much more cell apoptosis and activate p53 to a much greater degree, which in turn markedly increased expression of proapoptosis genes. The enhanced cytotoxic activity was partially blocked by
pifithrin- α , which might be through attenuating the increased apoptosis. Furthermore,
ocotillol significantly increased the antitumor activity of Dox in A549 xenograft
tumor in nude mice. These findings indicated that
ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent apoptosis and suggested that coadministration of
ocotillol with Dox might be a potential therapeutic strategy.