Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities

Tian, Meili; Yang, Shuang; Yan, Xinpeng

doi:10.1590/1414-431x20187151

Cited by 22 publications

(21 citation statements)

References 27 publications

(27 reference statements)

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“…For example, Ren et al showed that icariin inhibited osteosarcoma cell proliferation [26]. Similarly, icariin exerted suppressive effects on colon cancer cells [27], thyroid cancer cells [28] and ovarian cancer cells [29]. The induction of S-phase arrest and apoptosis were observed in medulloblastoma cells after treatment with icariin [30].…”

Section: Introductionmentioning

confidence: 99%

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

et al. 2019

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Background Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. Results Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. Conclusion These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.

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Section: Introductionmentioning

confidence: 99%

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

et al. 2019

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“…10 In addition, Tian et al reported that ICA reduced human colon carcinoma cell growth and metastasis activity. 13 In this study, we primarily identified that ICA inhibited the proliferation and invasion of SCC-9 and SCC-15 cells and suppressed the tumor growth in vivo. Our present study firstly revealed that ICA could impede the growth and metastasis of OSCC.…”

Section: Discussionmentioning

confidence: 92%

“…As previous researches reported, ICA has a variety of pharmacological benefits including anti-osteoporosis, 7 anti-cardiovascular, 8 antitumor 9,10 and organ protection. 11,12 Interestingly, ICA has been proved to suppress ovarian cancer, 9 thyroid cancer, 10 colon cancer 13 and osteosarcoma 14 via different signals. However, the anti-OSCC role of ICA has not been discussed yet.…”

Section: Introductionmentioning

confidence: 99%

<p>Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65</p>

Lei¹,

Shi

et al. 2020

OTT

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Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear. Methods: Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of tolllike receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo. Results: In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues. Conclusion: Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.

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“…P53 is an important tumor suppressor, and its overexpression leads to arrest of the cell cycle and promotion of the apoptosis of cancer cells. Thus, we could speculate that the overexpression of p53 might be involved in the anti-cancer potential of ICA [ 13 ], where cubosomal delivery has a potential role in improving efficacy by improving the cellular availability of ICA.…”

Section: Discussionmentioning

confidence: 99%

“…It has been established that ICA induces apoptosis and suppresses autophagy via the overexpression of autophagy-related p53 in breast cancer cells [ 11 ] and that it inhibits the invasion and migration of gastric cancer cells by the vasodilator-stimulated phosphoprotein via the Rac1 pathway [ 12 ]. Metastasis and growth of colon cancer was reported to be inhibited by enhancing p53 activity through the regulation of caspase and the imbalance of BCL-2/Bax [ 13 ]. In spite of the well-established anticancer potential of ICA, its therapeutic application is limited because of its poor solubility in the aqueous environment, which results in poor bioavailability (~0.1%) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Optimized Icariin Cubosomes Exhibit Augmented Cytotoxicity against SKOV-3 Ovarian Cancer Cells

Fahmy

Alhakamy

2020

Pharmaceutics

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Clinical application of icariin (ICA) is limited, despite its activity against cancer growth, because of the low solubility of ICA in an aqueous environment. Therefore, the present study attempted to develop and optimize ICA-loaded cubosome delivery and to explore its efficacy and possible mechanism of action against ovarian cancer. The optimization of the cubosome formulation was performed using the Box‒Behnken statistical design; during the characterization, the particle sizes were in the range of 73 to 183 nm and the entrapment efficiency was 78.3% to 97.3%. Optimized ICA-loaded cubosomes (ICA-Cubs) exhibited enhanced cytotoxicity and apoptotic potential, compared with ICA-raw, against ovarian cancer cell lines (SKOV-3 and Caov 3). The optimized ICA-Cubs showed a relatively non-cytotoxic effect on normal EA.hy926 endothelial cells. Further analysis of cell cycle arrest suggested a potential role in the pre-G1 and G2/M phases for ICA-Cubs in comparison with ICA-raw. ICA-Cubs increased the generation of reactive oxygen species (ROS) and the overexpression of p53 and caspase-3 in the SKOV-3 cell line. In conclusion, the cubosomal delivery of ICA might provide a prospective approach towards the superior control of ovarian cancer cell growth. Its improved efficacy compared with that of the free drug might be due to the improved solubility and cellular permeability of ICA.

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Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities

Cited by 22 publications

References 27 publications

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

<p>Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65</p>

Optimized Icariin Cubosomes Exhibit Augmented Cytotoxicity against SKOV-3 Ovarian Cancer Cells

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