生体分子研究と治療学ジャーナル

概要

Improving Doxorubicin-Chemotherapy Treatment with Luteolin and Resveratrol: A Novel Synthetically Engineered Secondary Metabolite "TDB-13" Created with Luteolin and Resveratrol

First-line chemotherapy drug doxorubicin, the most potent chemotherapy drug to date, is used in virtually all chemotherapy treatment plans. 92% of cancer patients are treated with chemotherapy yet for the past six decades, chemotherapy has had a failure rate of 90%. An overwhelming majority of the failures are attributed to the side effects of doxorubicin. No existing treatment exists that mitigates doxorubicin’s repercussions without significantly depleting its therapeutic efficacy.

While research indicates that secondary metabolites are improved when working with other chemicals/compounds and that luteolin and resveratrol specifically have protective effects on heart tissue (which could alleviate a major side effect: cardiotoxicity), no research has tested any secondary metabolites on any chemotherapy drug. To evaluate therapeutic efficacy: luteolin, resveratrol, and doxorubicin treated in vitro models of carcinoma (80%-90% of all cancer cases) alone and as a trio. To test the side effect of cardiotoxicity: Extracellular matrix components were coated onto the surface of cardiomyocytes.

Results of luteolin and resveratrol alone indicate that though they are therapeutic to in vitro carcinoma cells, there is one weakness: A small therapeutic window (concentrations of 15 μM and 20 μM being equally or less effective as the lowest concentrations of 5 μM and 10 μM) — suggesting that while luteolin and resveratrol have increased in popularity (in the form of dietary supplements) among cancer patients by 82% since 2010, the compounds may not always produce the desired effect. Combining luteolin and resveratrol with doxorubicin was able to improve therapeutic efficacy of doxorubicin while reducing cardiotoxicity. However, the weakness of a small therapeutic window still existed. By methylation and glycosylation of both luteolin and resveratrol, a novel compound that the present study named “TDB-13” was able to maintain the level of therapeutic efficacy and reduction of cardiotoxicity while lengthening the therapeutic window. Thus, new components to chemotherapy treatment can potentially improve it greatly.