Santin (5,7-Dihydroxy-3,6,4′-Trimetoxy-Flavone) Enhances TRAIL-Mediated Apoptosis in Colon Cancer Cells

Kłósek, Małgorzata; Jaworska, Dagmara; Pietsz, Grazyna; Szliszka, Ewelina

doi:10.3390/life13020592

Cited by 3 publications

(3 citation statements)

References 76 publications

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“…Induction of both apoptotic pathways by santin was previously reported in digestive system cancer cells ( Szoka et al, 2021 ). Moreover, activation of extrinsic pathway by increase in expression of TRAIL receptors (TRAIL-R1 and TRAIL-R2) was recently shown in santin treated colon cancer cells ( Kłósek et al, 2023 ). Although, santin similarly affected apoptosis pathways in both cell lines, a divergent effect was found at the level of p53.…”

Section: Discussionmentioning

confidence: 97%

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Szoka,

Nazaruk,

Giegiel

et al. 2023

Front. Mol. Biosci.

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Cancer of the corpus uteri and cervix uteri, collectively ranks second among new cancer cases in women after breast cancer. Therefore, investigation of new anticancer agents and identifying new molecular targets presents a challenge to improve effectiveness of chemotherapy. In this study, antiproliferative activity of flavonoids derived from the buds of silver birch and downy birch was evaluated in endometrial cancer Ishikawa cells and cervical cancer HeLa cells. It was found that flavanol santin reduced viability of both cell lines better than other flavonoids, including apigenin and luteolin. Moreover, this activity was slightly higher than that induced by the chemotherapy drug, cisplatin. Santin promoted intrinsic and extrinsic apoptosis pathways in cancer cells, but it had low toxicity in normal fibroblasts. The mechanisms of impairing cancer cell viability included induction of oxidative proline catabolism, however in different ways in the cell lines used. In HeLa cells, increase of proline oxidation was due to activation of p53 leading to proline oxidase upregulation. In contrast, in Ishikawa cells, having basal proline oxidase level significantly higher than HeLa cells, santin treatment decreased its expression. Nevertheless, proline oxidation was induced in these cells since santin increased expression and activity of prolidase, an enzyme providing proline from protein degradation. In both cell lines, proline oxidation was associated with generation of reactive oxygen species leading to reduction in cell viability. Our findings reveal the involvement of proline oxidase in induction of apoptosis by santin and identify a role of prolidase in proline oxidase-dependent apoptosis.

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Section: Discussionmentioning

confidence: 97%

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Szoka,

Nazaruk,

Giegiel

et al. 2023

Front. Mol. Biosci.

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“…The results against the typical cell line (MCF-10 cells) revealed a negligible cytotoxic effect. This effect of flavonoids and nanoflavonoids on NCF-7 and PC-3 cells may be indicative of a mechanism that inhibits proliferation by triggering apoptosis 35 . In contrast, MCF-10 showed no signs of such action.…”

Section: Anticancer Activity Of Compoundsmentioning

confidence: 92%

Isolation and Identification of Flavonoid Compounds from Euphorbia Milii Plant Cultivated in Iraq and Evaluation of its Genetic Effects on Two Types of Cancer Cell Line

Salman,

Alwash,

Kadhim

2024

Baghdad Sci.J

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The "crown of thorns" or Euphorbia milii, a decorative and therapeutic plant species, is regarded as belonging to the genus Euphorbia. E. milii is abundant in phenolic compounds, terpenoids, steroids and alkaloids. The main objective of this study was to investigate the extracted flavonoid and nano-flavonoids against two types of cell lines. Nano-flavonoids were synthesized via chitosan-maleic complex reaction. The structure of nano-flavonoids was analyzed by UV-sp -8001 spectrophotometer with a 200–1000 nm scanning wavelength and the produced compounds were examined. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are used to determine the morphological properties. A strong and cutting-edge anti-proliferative drug against breast cancer cells (MCF-7) and prostate cancer cells (PC3) is the flavonoid and nano-flavonoid. The anti-cancer efficacy of flavonoids and nano-flavonoids against two different cancer cell lines as well as healthy cell lines was examined using the MTT assay. DNA fragmentation and the AO/ EtBr double staining technique were used to examine apoptotic markers. To determine the dispersion of the cell cycle, flow cytometry was used. The recent findings showed that the quantities of flavonoid and nano-flavonoid considerably improved the cytotoxic effect against breast and prostate cancer cell lines. Additionally, the cell cycle arrest in the G0/G1 phase was linked to the apoptosis of the cell lines induced by flavonoids and nano-flavonoids. According to these results, flavonoids and nano-flavonoids prevent cancer cell lines from proliferating, which causes the cell cycle to be arrested and apoptosis to be induced. The available findings suggested that the flavonoid and nano-flavonoid complex would represent a promising therapeutic approach for treating cancer cells of other types.

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“…The potential toxicity of flavanone methyl-derivatives was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium (MTT) assay, as described in previous studies [48]. This assay relies on viable cells cleaving the tetrazolium salt MTT (provided by Sigma Chemical Company, St. Louis, MO, USA) to produce a blue formazan dye.…”

Section: Cell Viability Assaymentioning

confidence: 99%

In Vitro Anti-Inflammatory Activity of Methyl Derivatives of Flavanone

Kłósek,

Krawczyk-Łebek,

Kostrzewa-Susłow

et al. 2023

Molecules

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Inflammation plays an important role in the immune defense against injury and infection agents. However, the inflammatory chronic process may lead to neurodegenerative diseases, atherosclerosis, inflammatory bowel diseases, or cancer. Flavanones present in citrus fruits exhibit biological activities, including anti-oxidative and anti-inflammatory properties. The beneficial effects of flavanones have been found based on in vitro cell cultures and animal studies. A suitable in vitro model for studying the inflammatory process are macrophages (RAW264.7 cell line) because, after stimulation using lipopolysaccharide (LPS), they release inflammatory cytokines involved in the immune response. We determined the nitrite concentration in the macrophage cell culture and detected ROS using chemiluminescence. Additionally, we measured the production of selected cytokines using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. For the first time, we have shown that methyl derivatives of flavanone inhibit NO and chemiluminescence generated via LPS-stimulated macrophages. Moreover, the tested compounds at 1–20 µM dose-dependently modulate proinflammatory cytokine production (IL-1β, IL-6, IL-12p40, IL-12p70, and TNF-α) in stimulated RAW264.7 cells. The 2′-methylflavanone (5B) and the 3′-methylflavanone (6B) possess the strongest anti-inflammatory activity among all the tested flavanone derivatives. These compounds reduce the concentration of IL-6, IL-12p40, and IL12p70 compared to the core flavanone structure. Moreover, 2′-methylflavanone reduces TNF-α, and 3′-methylflavanone reduces IL-1β secreted by RAW264.7 cells.

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Santin (5,7-Dihydroxy-3,6,4′-Trimetoxy-Flavone) Enhances TRAIL-Mediated Apoptosis in Colon Cancer Cells

Cited by 3 publications

References 76 publications

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Isolation and Identification of Flavonoid Compounds from Euphorbia Milii Plant Cultivated in Iraq and Evaluation of its Genetic Effects on Two Types of Cancer Cell Line

In Vitro Anti-Inflammatory Activity of Methyl Derivatives of Flavanone

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