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ABSTRACT: Introduction
The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation.Materials and methods
The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 ?g/ml). Activated HSCs (aHSCs) were detected by ?-SMA and IL-6 mRNA expressions and cytokine arrays of HSC's culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression.Results
Colon cancer-CM significantly increased ?-SMA and IL-6 mRNA expressions of aHSC. ?-SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death.Conclusions
TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells.
SUBMITTER: Wada Y
PROVIDER: S-EPMC7733620 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Wada Yuma Y Tokuda Kazunori K Morine Yuji Y Okikawa Shohei S Yamashita Shoko S Ikemoto Tetsuya T Imura Satoru S Saito Yu Y Yamada Shinichiro S Shimada Mitsuo M
Oncotarget 20201208 49
<h4>Introduction</h4>The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation.<h4>Materials and methods</h4>The HSCs (LX2) were cultured in colon cancer cells (HCT116 and ...[more]