Icariin sensitizes human colon cancer cells to TRAIL‑induced apoptosis via ERK‑mediated upregulation of death receptors

Kim, Buyun; Seo, Ji Hae; Lee, Ki Yong; Park, Byoungduck

doi:10.3892/ijo.2020.4970

Cited by 16 publications

(18 citation statements)

References 34 publications

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“…Previous studies have shown that icariin can induce apoptosis of a variety of tumor cells, and reduce the invasion and migration of tumor cells, thus achieving anti-tumor effects [21,22]. Bu YK et al [23] found that icariin could promote apoptosis of human colon cancer cells in vivo and in vitro; their studies provided evidence that icariin sensitized tumor cells to TRAIL-induced apoptosis through reactive oxygen species (ROS), extracellular regulated protein kinases (ERK) and C/EBP homologus protein (CHOP)mediated upregulation of DR5 and DR4. Ji X et al [24] showed that icariin had no significant inhibitory effect on esophageal cancer cell proliferation in vitro, but could induce apoptosis in vivo through Fas expression and secretion of Fas-L and IFN-γ, thus playing an anti-esophageal cancer role.…”

Section: Discussionmentioning

confidence: 99%

Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway

Qian¹,

Zhu²,

Xu³

et al. 2021

EJGO

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To investigate the mechanism of icariin in promoting apoptosis of breast cancer cells by regulating the Phosphatidylinositol kinase (PI3K) PI3K/AKT signaling pathway mediated by Maternal embryonic leucine zipper kinase (MELK). Methods: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were used to detect the expression of MELK. small interfering RNA (siRNA)-MELK cell transfection technology was used to detect the correlation between MELK and PI3K/AKT. Different icariin concentrations on proliferation, migration and apoptosis of breast cancer cells were detected by flow cytometry, CCK-8, and Transwell. Western blot was used to detect the effects of icariin on MELK expression, AKT, cyclin, and apoptosis-related proteins. Results: Compared with normal mammary epithelial cells, the expression of MELK in breast cancer cells was significantly increased (p < 0.01). si-MELK decreased the expression of p-AKT, increased the expression of epithelial-mesenchymal transition (EMT)-related protein E-cadherin, and decreased the expression of N-cadherin and vimentin. Compared with the control group, icariin solution group showed a decrease in cell proliferation ability, a significant increase in cell apoptosis and a decrease in cell migration ability (p < 0.05). Icariin could induce G2/M arrest and inhibit the growth of breast cancer cells. Conclusion: Icariin can inhibit the expression of MELK, inhibit the PI3k/AKT signaling pathway to a certain extent, and further has a therapeutic effect on breast cancer.

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Section: Discussionmentioning

confidence: 99%

Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway

Qian¹,

Zhu²,

Xu³

et al. 2021

EJGO

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“…Also, histone deacetylase inhibitors (HDACi) and tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) represent other targeted anti-cancer therapeutic strategies [140,141]. HDACi is a novel class of smallmolecular therapeutics that target the regulation of histone and non-histone proteins [142].…”

Section: Flavonoids Enhance Effectiveness Of Targeted Anti-cancer Therapymentioning

confidence: 99%

“…Mutations in DR4 and DR5, domains of death receptors associated with TRAIL-induced apoptosis, induce cancer cell resistance to TRAIL. However, icariin (a prenylated flavonol glycoside derived from Epimedium sagittatum ) sensitized HCT116 colon cancer cells to TRAIL-induced apoptosis through the upregulation of DR5 and DR4 (mediated by ROS, ERK, and transcription factor CCAAT enhancer‑binding protein homologous protein/CHOP/) in vitro and in vivo (xenograft mouse model) [ 140 ].…”

Section: Resistance To Anti-cancer Treatmentsmentioning

confidence: 99%

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

et al. 2021

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Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are:- Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects;- Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

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“…Chinese medicine has been widely used to treat several types of malignant tumors. ICA, as a vital active ingredient of epimedium in Chinese medicine, serves an inhibitory role in the occurrence and development of malignant tumors; therefore, it has been widely used in the prevention and treatment of numerous types of cancer, such as cervical, ovarian, colon and triple-negative breast cancer (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF‑κB and PI3K/AKT pathways

Sun

Zhang

2021

Exp Ther Med

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Oral squamous cell carcinoma (OSCC), one of the most common types of human cancer, has a high mortality rate and a poor prognosis due to its high rates of recurrence and metastasis. In recent years, icariin (ICA) has been reported to play an important role in a variety of malignancies, such as gastric, colorectal, pancreatic and ovarian cancer. However, its role and mechanism in OSCC remains to be elucidated. The present study aimed to investigate the effect of ICA in OSCC cells and to reveal its underlying mechanisms. The OSCC cell lines SCC9 and Cal 27 were used to explore the effect of different concentrations of ICA on the biological behavior of OSCC cells. The effect of ICA on OSCC cell proliferation and apoptosis was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometric assays, respectively. Subsequently, the protein expression levels of caspase-3 and cleaved-caspase-3 were detected using western blot analysis. Additionally, the protein and mRNA expression levels of nuclear factor-κB (NF-κB) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway-related factors were determined using western blot analysis and reverse transcription-quantitative PCR, respectively. The results demonstrated that ICA inhibited OSCC cell proliferation and significantly increased the apoptosis rate in a dose-dependent manner. In addition, treatment of OSCC cells with ICA upregulated the protein expression of cleaved-caspase-3 and increased the cleaved-caspase-3/caspase-3 ratio. The protein expression levels of phosphorylated (p)-p65, p-PI3K and p-AKT were decreased in OSCC cells treated with ICA. The aforementioned findings revealed that ICA could attenuate the proliferation of OSCC cells and induce apoptosis via inhibiting the NF-κB and PI3K/AKT signaling pathways. Therefore, the current study provided a new insight into the clinical treatment of OSCC.

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Icariin sensitizes human colon cancer cells to TRAIL‑induced apoptosis via ERK‑mediated upregulation of death receptors

Cited by 16 publications

References 34 publications

Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway

Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF‑κB and PI3K/AKT pathways

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