Two hydroxyflavanones isolated from Scutellaria baicalensis roots prevent colitis-associated colon cancer in C57BL/6 J mice by inhibiting programmed cell death-1, interleukin 10, and thymocyte selection-associated high mobility group box proteins TOX/TOX2
| Autor: | Yoshiyuki Kimura, Maho Sumiyoshi |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Thymocytes Colon Dextran Sulfate Programmed Cell Death 1 Receptor Azoxymethane Pharmaceutical Science Apoptosis Colitis Interleukin-10 Mice Inbred C57BL Mice Complementary and alternative medicine Cyclooxygenase 2 HMGB Proteins Colonic Neoplasms Drug Discovery Tumor Microenvironment Animals Molecular Medicine Colitis-Associated Neoplasms Scutellaria baicalensis |
| Zdroj: | Phytomedicine. 100:154076 |
| ISSN: | 0944-7113 |
| DOI: | 10.1016/j.phymed.2022.154076 |
| Popis: | Colorectal cancer was the second leading cause of mortality in 2019 and the number of new colorectal cancer cases was the highest in 2018 and 2019 in Japan.The present study investigated the inhibitory effects of 2(S)-2',5,6',7-tetrahydroxyflavanone and 2 (R), 3(R)-2',3,5,6'-7-pentahydroxyflavanone on the incidence and growth of tumors in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated mice.The intraperitoneal administration of AOM (10 mg/kg) on day 0 induced colorectal carcinogenesis. Mice were given free and unlimited access to drinking water containing 1.5% (w/v) DSS on days 5 - 8, 30 - 33, and 56 - 57. They were orally administered tetra- and penta-hydroxyflavanones (10 and 30 mg/kg) for 10, 11, and 14 days followed by discontinuation intervals of 20 and 15 days. Cytokine, chemokine, programmed cell death-1 (PD-1), cyclooxygenase (COX)-2, and thymocyte selection-associated high mobility group box protein (TOX)/TOX2 expression levels were measured using their respective ELISA kits and an immunohistochemical analysis.The number and area of tumors decreased by 60.6 and 72.9% in mice administered 10 mg/kg tetra- and pentahydroxyflavanones, respectively, with reductions of 95.0 and 87.0% in Ki-67-positive cells, 91.7 and 92.7% in COX-2-postive cells, and 83.1 and 93.8% in TOX/TOX2-positive cells, respectively, in the colon. On the other hand, two tera- and pentahydroxyflavanone had no effect on p53 (a tumor suppressor by cell cycle arrest and apoptosis)-positive cells. The administration of 10 mg/kg tetra- and pentahydroxyflavanones to AOM/DSS-treated mice also resulted in decreases of 59.5 and 42.5% in IL-10 levels and 58.1 and 93.9% in PD-1 levels, respectively, in the colon.The inhibitory effects of tetra- and pentahydroxyflavanones on the growth of colon tumors in AOM/DSS-treated mice appear to be associated with decreases in the colon levels of IL-10 and PD-1 through the down-regulated expression of COX-2 and CD8 |
| Databáze: | OpenAIRE |
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