Antioxidant value and Antiproliferative Efficacy of Mitragynine and a Silane Reduced Analogue

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): $2.25{\pm}0.02$ mmol trolox / mmol and $1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and $IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and $IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > $100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.