Research Papers:

Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells

Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon and Hyun-Jeong Ko _

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Oncotarget. 2017; 8:41401-41411. https://doi.org/10.18632/oncotarget.17388

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Eun-Hye Hong1,*, Eun-Young Heo1,*, Jae-Hyoung Song1, Bo-Eun Kwon1, Jae-Young Lee1, Yaejeong Park4, Jinwoong Kim4, Sun-Young Chang2, Young-Won Chin5, Sang-Min Jeon3 and Hyun-Jeong Ko1,6

1Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea

2Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea

3Lab of Cancer Signaling and Metabolism Network, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Korea

4College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea

5College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Korea

6Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Yeongtong-gu, Suwon, Gyeonggi-do 16229, Korea

*These authors have contributed equally to this work

Correspondence to:

Hyun-Jeong Ko, email: [email protected]

Sang-Min Jeon, email: [email protected]

Keywords: trans-scirpusin A, colorectal cancer cells, AMPK, autophagy, apoptosis

Received: January 04, 2017     Accepted: March 30, 2017     Published: April 24, 2017


Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.

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