A preliminary study on anti-colorectal cancer effect and molecular mechanism of Aegiceras corniculatum extract

Abstract

Objective: To study the inhibitory effects on colorectal cancer (CRC) and the underlying mechanism of the petroleum ether extract of Aegiceras corniculatum leaves (PACL). Materials and Methods: The effect of PACL on the proliferation of CRC cell lines DLD-1, HT-29, and SW480 was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and colony-forming assay. And then, a wound-healing assay was used to measure the migration ability of three CRC cells. The cell cycle and apoptosis of three CRC cells were measured by PI/RNase staining and annexin V-FITC/double staining, respectively, and the intrinsic apoptosis pathway was studied by the Western blot. The anti-CRC effect of PACL in vivo was evaluated by HT-29 xenograft zebrafish embryos. Results: PACL inhibited cell viability and proliferation in DLD-1, HT-29, and SW480 cells in a dose- and time-dependent manner. PACL can inhibit cell migration in DLD-1 and SW480 cells but not in the less mobile phenotype cell HT-29. PACL treatment resulted in cell cycle arrest of DLD-1 and HT-29 cells in the G2/M phase. Moreover, PACL can induce apoptosis in all three CRC cells, which may be achieved by regulating the intrinsic apoptosis pathway mediated by mitochondria and the endoplasmic reticulum. Interestingly, the tumor sizes were decreased after treatment with PACL and PACL combined with fluorouracil in HT-29 xenograft zebrafish embryos. Conclusions: These findings suggested that PACL may exert its anti-CRC effect by inducing apoptosis through the intrinsic apoptosis pathway and show a significant anti-CRC effect in vitro and in vivo, so it might be potentially developed as an anti-CRC agent.

Keywords

• aegiceras corniculatum
• apoptosis
• cell cycle
• colorectal cancer
• zebrafish xenograft