A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy

作者：Chun Jaemoo; Kang Minseok; Kim Yeong Shik^*

来源：Tumor Biology, 2014, 35(12): 12021-12030.

DOI：10.1007/s13277-014-2501-0

• Triterpenoid saponin
• Adenophora triphylla var. japonica
• Apoptosis
• Autophagy
• SB202190
• AGS cells

In the present study, we investigated the effects of 3-O-beta-D-galactopyranosyl-(1 -> 2)-[beta-D-xylopyranosyl-(1 -> 3)]-beta-D-glucuronopyranosyl-28-O-[alpha-L-arabinopyranosyl-(1 -> 4)-alpha-L-arabinopyranosyl-(1. 3)-beta-D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-fucopyranosyl] quillaic acid, named compound 1, on the induction of apoptosis and autophagy in human gastric cancer AGS cells. Compound 1, a triterpenoid saponin isolated from the root of Adenophora triphylla var. japonica, effectively inhibited the growth of AGS cells by inducing apoptosis, as well as autophagy. Apoptosis by compound 1 treatment was associated with activation of caspases, release of cytochrome c, and increased ratio of Bax/Bcl-2. Autophagy by compound 1 treatment was indicated by LC3-II protein expression. We also found an increase in phosphorylation of p38 and JNK and a decrease in phosphorylation of ERK and Akt after compound 1 treatment. Furthermore, pretreatment with p38 inhibitor SB202190 completely inhibited compound 1-induced activation of caspases and cleavage of PARP1, whereas pretreatment with SB202190 synergistically increased the protein expression of LC3-II. These results suggest that compound 1 distinctly induces apoptotic and autophagic cell death and the increased autophagy by SB202190 protects compound 1-induced AGS cell death. Our findings provide an important clue for exploring the potential anticancer role of compound 1.

• 出版日期2014-12