Preclinical efficacy of a carboxylesterase 2-activated prodrug of doxazolidine.

Doxazolidine (Doxaz) is a functionally distinct formaldehyde conjugate of doxorubicin (Dox) that induces cancer cell death in Dox-sensitive and resistant cells. Pentyl PABC-Doxaz (PPD) is a prodrug of Doxaz that is activated by carboxylesterase 2 (CES2), which is expressed by liver, non-small-cell lung, colon, pancreatic, renal, and thyroid cancer cells. Here, we demonstrate that in two murine models, PPD was effective at slowing tumor growth and demonstrated markedly reduced cardiotoxic and nephrotoxic effects, as well as better tolerance, relative to Dox.

Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappaB-mediated inducible chemoresistance.

The acute and cumulative dose-related toxicity and drug resistance, mediated via nuclear factor kappaB (NFkappaB), of anthracycline anticancer drugs pose a major problem in cancer chemotherapy. Here, we report that oral silibinin (a flavanone) suppresses human non-small-cell lung carcinoma A549 xenograft growth (P = 0.003) and enhances the therapeutic response (P < 0.

Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells.

With an approach to enhance the efficacy of chemotherapy agents against breast cancer treatment, here, we investigated the anti-cancer effects of grape seed extract (GSE) and doxorubicin (Dox), either alone or in combination, in estrogen receptor-positive MCF-7 and receptor-negative MDA-MB468 human breast carcinoma cells. GSE (25-200 micro g/ml) treatment of cells resulted in 16-72% growth inhibition and 9-33% cell death, in a dose- and a time-dependent manner. In other studies, Dox (10-100 nM) treatment showed 23-96% growth inhibition and 10-55% cell death.

Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells.

Significant emphasis is being placed on combination chemotherapy of cancer using cytotoxic agents and naturally occurring chemopreventive agents, having different mechanisms of action with non-overlapping toxicity. In this regard, here we assessed whether a cancer preventive agent silibinin synergizes the therapeutic potential of doxorubicin (Dox), cisplatin or carboplatin, the chemotherapeutic drugs, in both estrogen-dependent and -independent human breast carcinoma, MCF-7 and MDA-MB468 cells, respectively. When tested alone, each of the four agents showed growth inhibition in both the cell lines in a dose- and a time-dependent manner.

Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis.

Purpose: We recently demonstrated the strong anticancer efficacy of silibinin,an active constituent of a widely consumed dietary supplement milk thistle extract, against human prostate cancer cells in culture and nude mice xenografts. We also observed that pharmacologically achievable concentrations of silibinin in animal studies were in the range of 25-100 microM, depending on the dose regimen, which did not show any apparent toxicity to the animals. In this study, we assessed whether silibinin synergizes the therapeutic potential of the chemotherapeutic drug doxorubicin against prostate cancer, the effectiveness of which is limited because of high systemic toxicity.

Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels.

We have reported recently the anticancer effect of flavonoid antioxidant silymarin, the major part of milk thistle extract, against advanced human prostate carcinoma DU145 cells (X. Zi et al., Cancer Res.