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This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the most promising extract. Ethanolic extracts from the leaves of 14 Passiflora species were obtained by accelerated solvent extraction and in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single concentration of 50 μg/ml. Additionally, the IC 50 of the Passiflora alata (ELPA) leaf extracts was determined against both cancer (HCT-116, SF-295, OVACAR-8, and HL-60), and non-cancer cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. The morphological analyses, using light and fluorescence microscopy, and cell cycle and DNA fragmentation analysis, using flow cytometry, were evaluated to study the mechanism of cell death induced by ELPA in HL-60 cells. Among the Passiflora leaf extracts evaluated; ELPA stood out with high cytotoxic activity, followed by Passiflora capsularis and Passiflora quadrangularis with varying high and low cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC 50 19.37 μg/ml), and without cytotoxicity against PBMC, suggesting selectivity for cancer cells. The cytotoxic activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in the G 2 /M phase. From among the studied species, ELPA presented greater cytotoxic activity, possibly a consequence of synergistic flavonoid action, which induces cell death by apoptosis and necrosis.

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