Effects of Binúñga [Macaranga tanarius (L.) Müll.Arg.] Crude Leaf Extract on Cancer Cells, Angiogenesis, Early Implantation, and Embryogenesis

Abstract

Medicinal plants have long been known to contain an abundance of natural bioactive compounds, some of which have been studied for their anti-cancer and anti-angiogenic properties. However, testing the possible side effects of a “drug” candidate is not congruently done in vivo. Hence, the effects of these plant extracts on different biological processes are unknown. This study aims to evaluate the anti-cancer and anti-angiogenic activity of the crude leaf extract of the plant Macaranga tanarius (L.) Müll.Arg. while simultaneously assessing its safety. For anti-cancer and anti-angiogenic evaluation of the extract, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide] and duck chorioallantoic membrane (CAM) assays were utilized, respectively. Alongside this, the detrimental effect of the leaf extract on normal biological processes was conducted by examining its effect on mice implantation and embryogenesis through morphological and histological analyses. For anti-cancer potential, crude methanolic extract of the leaves from M. tanarius was found to be cytotoxic against HCT116 at a concentration of 18.93 ug/mL. The extract also showed anti-angiogenic potential as CAM assay revealed that the extract reduced the percent area of blood vessels. In the mice implantation assay, the methanolic extracts were not able to significantly decrease the number of embryo implantations in the uterus. Furthermore, CD31 staining showed that the uterus treated with M. tanarius exhibited a significant reduction in blood vessels. Reduction of blood vessels did not affect late organogenesis since the gestation index of dams and fetal malformation index showed no significant difference between PBS- (phosphate-buffered saline solution) and extract-treated groups after additional treatment at (embryonic day) E8.5 and E9.5. This suggests that M. tanarius leaves possess bioactive compounds for anti-cancer and anti-angiogenic therapy that may not interfere with normal biological processes such as pregnancy