Antitumor effect and apoptosis induction of Alocasia cucullata (Lour.) G. Don in human gastric cancer cells in vitro and in vivo

Abstract

Background: Alocasia cucullata (Lour.) G. Don was applied in traditional Chinese medicine for the treatment of cancer in Chinese Southwest area. Its antitumor effect was scrutinized in vitro and in vivo. And for the first time, the mechanism of extract of A. cucullata (EAC) against human gastric cancer cell was well examined. Methods: To detect the most effective fraction, the antiproliferation efficacy of four fractions (namely derivatives by adding EAC to n-BuOH, petroleum ether, EtOAc and water until dissolve fully) against five cancer cell lines were screened by MTT assay. Among four fractions, the IC50s of n-BuOH fraction of EAC (EAC-B) against the five cell lines and time-dependent inhibition to gastric cancer cell line (MGC-803) were further investigated (MTT assay). In vivo antitumor efficacy of EAC-B was examined by MGC-803 bearing tumor nude mice. Especially, the paper focused on the relevant mechanism study of EAC-B against MGC-803 included cell cycle distribution (flow cytometry) and cyclin D1 expression (RT-PCR and western blot), apoptosis (Hoechst 33342 stain and flow cytometry), apoptosis-related protein expression (Akt, p-Akt, ERK, p-ERK, Bcl-2, Bax) by western blot, and caspase3/7 activity assay. Results: EAC-B showed its cytotoxicity against various tumor cell lines, particularly against gastric cancer cells with IC50 value of 18.8 μg/mL in vitro. Tumor weight was significantly reduced by EAC-B in vivo. In the mechanism study, EAC-B increased cell ratio at G0/G1 phase and reduced cyclin D1 expression both at protein and mRNA level on MGC-803. Chromatin condensation and apoptosis were also observed. EAC-B down-regulated p-Akt, p-ERK expression and up-regulated Bax/Bcl-2 ratio. Further, caspase 3/7 activation was enhanced as well. Conclusions: This study demonstrated that EAC-B had potent antitumor activity both in vitro and in vivo. Its mechanism is primarily via antiproliferation of G0/G1 arrest and cell pro-apoptosis, including PI-3 K/Akt pathway, ERK activity, stimulated cytochrome C release and caspase 3/7 activity accompanied with an increase of Bax/Bcl-2 ratio. EAC-B may be a potential source of novel compounds for gastric cancer treatment.