Sudachitin, a polymethoxyflavone from Citrus sudachi, induces apoptosis via the regulation of MAPK pathways in human keratinocyte HaCaT cells

Abe, Shogo; Yuasa, Keizo

doi:10.1016/j.bbrc.2019.09.010

Cited by 6 publications

(10 citation statements)

References 28 publications

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“…Although 3% SPE significantly inhibited serum-stimulated proliferation of HaCaT cells, sudachitin showed no inhibition of growth even at a higher concentration (1 µM) ( Figure 5 A). However, in a concentration of 30 µM, it inhibited proliferation, consistent with a previous result [ 17 ].…”

Section: Resultssupporting

confidence: 92%

“…We previously reported that sudachitin, a polymethoxyflavone isolated from the peel of C. sudachi , suppressed proliferation and induced apoptosis of HaCaT cells at 30 µM [ 17 ]. Thus, we examined whether sudachitin could suppress keratinocyte proliferation at a concentration in 3% SPE (0.46 µM, Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Sudachitin at 30 µM also suppressed the ERK pathway in HaCaT cells [ 17 ]. Because the peel of C. sudachi contains many phenolic compounds, including hesperidin, naringin, narirutin, and sudachitin ( Table 1 ), we attempted to identify active compound(s) that could affect the ERK pathway in keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Cell proliferation was measured with the 5-bromo-2′-deoxyuridine (BrdU) incorporation assay using a CycLex Cellular BrdU ELISA Kit Ver.2 (Medical & Biological Laboratories Co., Ltd., Nagoya, Japan) as previously described [ 17 ]. In brief, HaCaT cells were plated at a density of 7 × 10 3 per well on a 96-well plate and were serum-starved for 24 h. Next, the cells were pretreated with 3% SPE for 1 h and were treated with either 3% FBS or 1 nM EGF (diluted with DMEM including 0.5% FBS) for 24 h. For NHEKs, cells were plated at a density of 4 × 10 3 per well on a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…After 24 h, the cells were serum-starved for 2 h and treated with 3% SPE for 1 h; then, they were stimulated with 1 nM EGF for an additional 6 h. The cells were lysed and subjected to the luciferase reporter assay. The luciferase and β-galactosidase activities were measured using a Sirius luminometer (Berthold Detection Systems GmbH, Pforzheim, Germany) as previously described [ 17 ]. Luciferase activity was normalized to β-galactosidase activity.…”

Section: Methodsmentioning

confidence: 99%

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Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

et al. 2020

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Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

et al. 2020

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Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf‐2/Keap‐1, Inflammatory, Steroidogenic, and Histological Profile

Ijaz,

Imtiaz,

Hayat

et al. 2024

Environmental Toxicology

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Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ‐induced testicular toxicity in rats. Forty‐eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap‐1 while downregulating the expression of 3‐beta hydroxysteroid dehydrogenase (3β‐HSD), 17‐beta hydroxysteroid dehydrogenase (17β‐HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), nuclear factor‐kappa B (NF‐κB), interleukin‐1beta (IL‐1β), and cyclooxygenase‐2 (COX‐2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate‐specific proteases‐3 (Caspase‐3) and Bcl‐2‐associated X‐protein (Bax) while downregulating the expressions of B‐cell lymphoma‐2 (Bcl‐2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti‐inflammatory, and androgenic potential.

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Proteomics-Based Network Pharmacology and Molecular Docking Reveal the Potential Mechanisms of 5,6,7,4'-Tetramethoxyflavone Against Hela Cancer Cells

You,

Li,

Ding

et al. 2024

Preprint

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Sudachitin, a polymethoxyflavone from Citrus sudachi, induces apoptosis via the regulation of MAPK pathways in human keratinocyte HaCaT cells

Cited by 6 publications

References 28 publications

Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf‐2/Keap‐1, Inflammatory, Steroidogenic, and Histological Profile

Proteomics-Based Network Pharmacology and Molecular Docking Reveal the Potential Mechanisms of 5,6,7,4'-Tetramethoxyflavone Against Hela Cancer Cells

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