Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo

Abstract

AbstractGlioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of Tapirira guianensis and its antitumor potential (in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 µg/mL, 83.07 µg/mL, 59.27 µg/mL and U251 with IC50 25.92 µg/mL, 37.3 µg/mL and 18.84 µg/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 – 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 – 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo. The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation.