Inhibition of Colon Cancer Cells Proliferation and Invasion by Etoposide Loaded on Nano-Suspensions Containing Black Currant Seed and Evening Primrose Oils

Abstract

Formulating etoposide into a nanoemulsion based on combining two natural oils, Ribes nigrum (black currant) seed oil and organic evening primrose oils may improve its antineoplastic activity in cancer cells. The present study aimed to synthesize, characterize and in vitro evaluate the cytotoxic effect of formulating etoposide-loaded (black currant) seed oil and organic evening primrose oils on Colorectal Carcinoma colon cancer cells. The anti-proliferation and anti-invasion effects of the produced formula on Colorectal Carcinoma were investigated by the cell counting kit-8 and the collagen-based cell invasion assay, respectively. Mitochondrial staining kit, annexin Fluorescein isothiocyanate double staining, and nucleosome detection were used to discriminate the stages of apoptosis. According to the dynamic light scattering results, formulating etoposide-loaded (black currant) seed oil consisted of nanodroplets with z-average diameters of 144.6±5.3 nm and mean surface charge of -0.081±0.001 mV. Only (1.7±1.3) µM of formulating etoposide-loaded (black currant) seed oil was able to cause 50 % reduction in the Colorectal Carcinoma cellular growth which was strikingly lower than that of free- formulating etoposide (18.1±2.5 µM) by around ten-fold. The superior apoptotic effect of Formulating etoposide Ribes nigrum (black currant) seed oil and organic evening primrose oils relative to free- formulating etoposide on the Colorectal Carcinoma cells was ascertained by the enhanced mitochondrial depolarization, higher nucleosomal ratio and increased amount of early and late apoptotic cellular populations. The Formulating etoposide Ribes nigrum (black currant) seed oil and organic evening primrose oils treatment impeded the invasion of colorectal carcinoma cells by (54.8±1.2) %, which was greater than the free- formulating etoposide treatment that deterred only (35.1±1.2) % of the invaded cells. In conclusion, the incorporation of formulating etoposide into a nanoemulsion formulated from the bioactive natural oils potentiates its antitumor activity in colon cancer cells.