Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from uncaria tomentosa bark on human ewing's sarcoma and breast cancer cell lines

Preparations from Uncaria tomentosa, a South American Rubiaceae, have been used in the Peru- vian traditional medicine for the treatment of in- fective, inflammatory and tumoral processes. In this study, the pentacyclic oxindole alkaloid mi- traphylline was isolated from the dried inner bark of this plant species, and its structure elucidated by analysis of NMR spectroscopic data. Mitraphyl- line was differentially identified from its stereoisomeric pair isomitraphylline by 15N‑NMR. Its antiproliferative and cytotoxic effects have been tested on human Ewingʼs sarcoma MHH‑ES‑1 and breast cancer MT-3 cell lines, using cyclo- phosphamide and vincristine as reference con- trols. A Coulter counter was used to determine viable cell numbers, followed by the application of the tetrazolium compound MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)- 2-(4-sulfophenyl)-2H-tetrazolium] an inner salt. A colorimetric method was employed to evaluate cell viability in this cytotoxic assay. Micromolar concentrations of mitraphylline (5 µM to 40 µM) inhibited the growth of both cell lines in a dose- dependent manner. The IC50 ± SE values were 17.15 ± 0.82 µM for MHH‑ES‑1 and 11.80 ± 1.03 µM for MT-3 for 30 hours, smaller than those obtained for the reference compounds. This ac- tion suggests that the pentacyclic oxindole alka- loid mitraphylline might be a new promising agent in the treatment of both human sarcoma and breast cancer.