Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells.

Tytuł:: Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells.
Autorzy:: Khan MI; Department of Biotechnology, Faculty of Biomedical and Life Sciences, Kohsar University, Murree 47150, Pakistan.
Karima G; Department of Bionanotechnology, Graduate School, Hanyang University, Seoul 04763, Korea.
Khan MZ; Department of Biotechnology, Chonnam National University, Yeosu 59626, Korea.
Shin JH; Department of Biotechnology, Chonnam National University, Yeosu 59626, Korea.
Kim JD; Department of Biotechnology, Chonnam National University, Yeosu 59626, Korea.; Research Center on Anti-Obesity and Health Care, Chonnam National University, Yeosu 59626, Korea.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2022 Sep 14; Vol. 23 (18). Date of Electronic Publication: 2022 Sep 14.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Proto-Oncogene Proteins c-akt*/metabolism
Saponins*/pharmacology
Saponins*/therapeutic use
Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Animals ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Caspase 3/metabolism ; Endothelial Cells/metabolism ; HEK293 Cells ; Humans ; Inflammation/drug therapy ; Interleukin-6/metabolism ; Mammals/metabolism ; NF-kappa B/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Tea ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; bcl-2-Associated X Protein/metabolism
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Contributed Indexing:: Keywords: IL-1β; NRF-2; apoptosis; cytotoxicity; inflammation; saponins
Substance Nomenclature:: 0 (Angiogenesis Inhibitors)
0 (Anti-Inflammatory Agents)
0 (Antioxidants)
0 (Interleukin-6)
0 (NF-kappa B)
0 (Reactive Oxygen Species)
0 (Saponins)
0 (Tea)
0 (Tumor Necrosis Factor-alpha)
0 (Vascular Endothelial Growth Factor A)
0 (bcl-2-Associated X Protein)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 3.4.22.- (Caspase 3)
Entry Date(s):: Date Created: 20220923 Date Completed: 20220926 Latest Revision: 20231028
Update Code:: 20240104
PubMed Central ID:: PMC9504392
DOI:: 10.3390/ijms231810665
PMID:: 36142578
: Czasopismo naukowe

Pełny tekst

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 ( Bcl-2 )-associated X protein ( BAX ) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B ( AKT ), vascular endothelial growth factor receptor-2 ( VEGFR-2 ), and nuclear factor kappa B ( NF-κB ). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.

Erratum in: Int J Mol Sci. 2023 Oct 16;24(20):. (PMID: 37895178)

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