Gamma-Irradiated Chrysin Improves Anticancer Activity in HT-29 Colon Cancer Cells Through Mitochondria-Related Pathway

Song, Ha Yeon; Kim, Hye Min; Mushtaq, Sajid; Kim, Woo Sik; Kim, Young Jun; Lim, Seung Taik; Byun, Eui Baek

doi:10.1089/jmf.2018.4320

Cited by 19 publications

(12 citation statements)

References 35 publications

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“…Chrysin, as an interfacial inhibitor of the COMP/TAGLN complex, may regulate tumors through a variety of pathways. Chrysin exhibits antitumor effects by inhibiting cell proliferation 30 , inducing apoptosis 31 , eliminating reactive oxygen species, and preventing angiogenesis 32 , 33 , but its direct target remains unknown 34 , 35 . Chrysin can directly act on the COMP/TAGLN interaction interface and inhibit mesenchymal transformation, thereby hindering the malignant progression of colorectal cancer (Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Zhong

Hou

et al. 2020

Theranostics

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Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum , was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

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Section: Discussionmentioning

confidence: 99%

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Zhong

Hou

et al. 2020

Theranostics

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“…CM1 isolated from gamma-irradiated chrysin was prepared in accordance with a previously described protocol [24]. Briefly, chrysin-methanol solution was irradiated at a dose of 50 kGy (10 kGy/h) using a cobalt-60 irradiator (point source AECL; IR-221; MDS Nordion International Co., Ltd., Ottawa, ON, Canada).…”

Section: Cm1 Preparationmentioning

confidence: 99%

“…In our previous study, we identified a new chrysin derivative (CM1) which exhibited greater anti-inflammatory activity in dendritic cells than chrysin and exerted protective effects in a mouse colitis model [23]. We had previously identified that CM1 is a hydroxyethyl derivative of chrysin that is produced by ionizing radiation from chrysin methanolic solution (Figure 1a) [24]. However, the mechanism underlying the anti-inflammatory effect of CM1-mediated negative regulation of TLR signaling has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

et al. 2021

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Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1.

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“…Irradiation substantially enhances the cytotoxic activity of chrysin. This inhibitory effect against colon cancer cells is exerted via promoting ROS generation, inducing mitochondrial dysfunction, activation of a caspase cascade (caspase-3 and caspase-9), and stimulating cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) [ 235 ].…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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Gamma-Irradiated Chrysin Improves Anticancer Activity in HT-29 Colon Cancer Cells Through Mitochondria-Related Pathway

Cited by 19 publications

References 35 publications

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

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