Identification of Growth Factors, Cytokines and Mediators Regulated by Artemisia annua L. Polyphenols (pKAL) in HCT116 Colorectal Cancer Cells: TGF-beta 1 and NGF-beta Attenuate pKAL-Induced Anticancer Effects via NF-?B p65 Upregulationopen access
- Jung, Eun Joo; Paramanantham, Anjugam; Kim, Hye Jung; Shin, Sung Chul; Kim, Gon Sup; Jung, Jin-Myung; Hong, Soon Chan; Chung, Ky Hyun; Kim, Choong Won; Lee, Won Sup
- Issue Date
- Artemisia annua L. polyphenols; anticancer effect; colorectal cancer; antibody array; cytokine; TGF-beta 1; NGF-beta; NF-KB p65
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, no.3
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- The anticancer effects of natural phytochemicals are relevant to the modulation of cytokine signaling pathways in various cancer cells with stem-like properties as well as immune cells. The aim of this study was to elucidate a novel anticancer mechanism of Artemisia annua L. polyphenols (pKAL) involved in the regulation of growth factors, cytokines and mediators in stem-like HCT116 colorectal cancer cells. Through RayBiotech human L-1000 antibody array and bioinformatics analysis, we show here that pKAL-induced anticancer effects are associated with downregulation of growth factor and cytokine signaling proteins including TGFA, FGF16, PDGFC, CCL28, CXCR3, IRF6 and SMAD1. Notably, we found that TGF-beta signaling proteins such as GDF10, ENG and TGFBR2 and well-known survival proteins such as NGF-beta, VEGFD and insulin were significantly upregulated by pKAL. Moreover, the results of hematoxylin staining, cell viability assay and Western blot analysis demonstrated that TGF-beta 1 and NGF-beta attenuated pKAL-induced anticancer effects by inhibiting pKAL-induced downregulation of caspase-8, NF-kappa B p65 and cyclin D1. These results suggest that certain survival mediators may be activated by pKAL through the TGF-beta 1 and NGF-beta signaling pathways during pKAL-induced cell death and thus, strategies to inhibit the survival signaling are inevitably required for more effective anticancer effects of pKAL.
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- 수의과대학 > Department of Veterinary Medicine > Journal Articles
- College of Medicine > Department of Medicine > Journal Articles
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