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

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Tumor Biology

Abstract

In the present study, we investigated the effects of 3-O-β-d-galactopyranosyl-(1 → 2)-[β-d-xylopyranosyl-(1 → 3)]-β-d-glucuronopyranosyl-28-O-[α-l-arabinopyranosyl-(1 → 4)-α-l-arabinopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-β-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.

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Acknowledgments

This work was supported by a Medical Research Center (MRC) grant funded by the National Research Foundation of Korea (No. 2009–93146).

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Authors and Affiliations

  1. Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea

    Jaemoo Chun, Minseok Kang & Yeong Shik Kim

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  1. Jaemoo Chun
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  2. Minseok Kang
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  3. Yeong Shik Kim
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Correspondence to Yeong Shik Kim.

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Chun, J., Kang, M. & Kim, Y.S. A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy. Tumor Biol. 35, 12021–12030 (2014). https://doi.org/10.1007/s13277-014-2501-0

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  • DOI: https://doi.org/10.1007/s13277-014-2501-0

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