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1.
Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin‐mediated protection from BPA‐associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen‐receptor‐positive MCF‐7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF‐7 cells. Meanwhile, BPA‐induced upregulation of oncogenic miR‐19a and miR‐19b, and the dysregulated expression of miR‐19‐related downstream proteins, including PTEN, p‐AKT, p‐MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR‐19 in BPA‐mediated MCF‐7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR‐19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA‐associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast‐cancer‐promoting effect as well as its target intervention. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

2.
Matrine (MAT) is an alkaloid in the dried roots of Sophora flavescens. The antitumor activity has been testified in colon cancer. Howbeit, the latent mechanism is still indistinct. The research probed the antitumor mechanism of MAT in colon cancer cells. MAT (0.25, 0.5, 0.75, 1, and 1.25 mM) was utilized to stimulate SW480 and SW620 cells for 24, 48, and 72 hr. Cell viability, apoptosis, cell cycle, and the correlative proteins were assessed via Cell Counting Kit‐8, flow cytometry, and Western blot. microRNA‐22 (miR‐22) in MAT‐treated or miR‐22‐silenced cells was estimated via real‐time quantitative polymerase chain reaction. The functions of miR‐22 inhibition were reassessed. Western blot was conducted for quantifying β‐catenin, MEK, and ERK. Luciferase reporter assay was done for confirming the targeting relationship between miR‐22 and ERBB3 or MECOM. MAT prohibited cell viability, accelerated apoptosis, and triggered cells cycle stagnation at G0/G1 phase. Additionally, miR‐22 was elevated by MAT; meanwhile, the influences of MAT were all inverted by miR‐22 inhibitor. MAT enhanced the expression of miR‐22, thereby obstructing Wnt/β‐catenin and MEK/ERK pathways. miR‐22 had a potential to target mRNA 3'UTR of ERBB3 and MECOM. These discoveries manifested that MAT could evoke colon cancer cell apoptosis and G0/G1 cell cycle arrest via elevating miR‐22.  相似文献   

3.
Type 1 diabetes mellitus (T1DM) is a systemic disease and one classical type of total DM. Bilobalide (BB) is constituted of EGb 761. Our purpose was identifying the role of BB in TIDM in the current study. MIN6 cells were treated by TNF‐α; then, viability, apoptosis, and insulin secretion were assessed by performing Cell Counting Kit‐8 assay, flow cytometry, glucose‐stimulated insulin secretion assay, and western blot. The effects of BB were assessed to identify its function. Further, the above mentioned parameters were reassessed when silencing miR‐153. TNF‐α declined viability and insulin secretion as well as raised apoptosis and inducible nitric oxide synthase (iNOS) expression in MIN6 cells. BB alleviated the apoptosis and dysfunction induced by TNF‐α. MiR‐153 expression was elevated by BB when induced by TNF‐α. Increase of viability and insulin secretion as well as decline of apoptosis and iNOS induced by BB treatment was alleviated by silencing miR‐153. The rates of p/t‐p70S6K, p/t‐mammalian target of rapamycin (mTOR) and p/t‐adenosine monophosphate‐activated protein kinase (AMPK) were raised by BB and suppressed by silencing miR‐153 under TNF‐α induced condition. BB raised viability and insulin secretion, declined apoptosis and iNOS expression by up‐regulating miR‐153. Furthermore, BB activated AMPK/mTOR pathway by up‐regulating miR‐153.  相似文献   

4.
Hypertension is recognized to be associated with low‐grade inflammation. Baicalin (BAI) is reported to possess various pharmacological including anti‐inflammatory activities. This research explored the molecular mechanism by which BAI functions in human aortic endothelial cells (HAECs). HAECs were pretreated with BAI. Cell viability, apoptosis, and expressions of crucial proteins were respectively evaluated using cell counting kit‐8 assay, flow cytometry, and western blot. Productions of cytokines were respectively assessed employing quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Cell transfection was utilized to alter miR‐145 expression. The expressions of proteins participated in JNK and p38MAPK pathways were analyzed utilizing western blot. TNF‐α inducement successfully evoked inflammatory injury in HAECs, exhibiting as prominently suppressed viability, while facilitated apoptosis and productions of cytokines. However, BAI pretreatment significantly ameliorated TNF‐α‐triggered inflammatory injuries. Besides, miR‐145 expression was markedly inhibited by TNF‐α inducement, while notably elevated by BAI pretreatment. Although miR‐145 overexpression had no significant influence on apoptosis, miR‐145 silence observably reversed BAI pretreatment‐evoked protective influences on TNF‐α‐induced HAECs, as well as the inhibited impacts on the levels of key proteins involved in JNK and p38MAPK pathways. This investigation illustrated that BAI relieved TNF‐α‐triggered injuries through upregulating miR‐145 via suppressing JNK and p38MAPK pathways.  相似文献   

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6.
Vitexin, identified as apigenin‐8‐C‐D‐glucopyranoside, a natural flavonoid compound found in certain herbs such as hawthorn herb, has been reported to exhibit anti‐oxidative, anti‐inflammatory, anti‐metastatic and antitumor properties. The aim of this study was to investigate the possible existence of p53‐dependent pathway underlying vitexin‐induced metastasis and apoptosis in human oral cancer cells, OC2 cells. Vitexin decreased cell viability significantly. Meanwhile, the expression of tumor suppressor p53 and a small group of its downstream genes, p21 WAF1 and Bax, were upregulated. The p53 inhibitor pifithrin‐α (PFT‐α) knockdown of the signaling of p53 led vitexin to lose its antitumor effect and inhibited the expression of p53 downstream genes, p21WAF1 and Bax. Vitexin had anti‐metastatic potential accompanied with increasing plasminogen activator inhibitor 1 (PAI‐1) accumulation and decreasing matrix metalloproteinase‐2 expression. Our present study evidenced, by using p53 inhibitor PFT‐α, PAI‐1 and peroxisome proliferator‐activated receptor γ are downstream genes of p53 in vitexin‐induced signaling. MAPK inhibitor PD98059 decreased the OC2 cells viability significantly. The expression of p53 and its downstream genes p21 WAF1 and Bax were enhanced by blocking the activation of p42/p44 MAPK in response to treatment with vitexin. Moreover, p42/p44 MAPK played a negative role in p53‐dependent metastasis and apoptosis. We give evidence for the first time that the novel p53‐dependent metastatic and apoptotic pathway induced by vitexin in human oral cancer OC2 cells. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

7.
Betula platyphylla (BP) is frequently administered in the treatment of various human diseases, including cancers. This study was undertaken to investigate the pharmacological function of the active components in BP and the underlying mechanism of its chemotherapeutic effects in human lung cancer cells. We observed that BP extracts and 1,7‐bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one (BE1), one of the components of BP, effectively decreased the cell viability of several lung cancer cell lines. BE1‐treated cells exhibited apoptosis induction and cell cycle arrest at the G2/M phase. Further examination demonstrated that BE1 treatment resulted in suppression of autophagy, as evidenced by increased protein expression levels of both LC3 II and p62/SQSTM1. Interestingly, the pharmacological induction of autophagy with rapamycin remarkably reduced the BE1‐induced apoptosis, indicating that apoptosis induced by BE1 was associated with autophagy inhibition. Our data also demonstrated that BE1 exposure activated the p38 pathway resulting in regulation of the pro‐apoptotic activity. Taken together, we believe that BE1 is a potential anticancer agent for human lung cancer, which exerts its effect by enhancing apoptosis via regulating autophagy and the p38 pathway.  相似文献   

8.
Silibinin, a flavonoid compound, has shown to be of chemopreventive potential against many cancers. However, its efficacy against gastric cancer has not been well elucidated. Here, we assessed the activity of Silibinin on apoptosis and cell‐cycle arrest in human gastric cells culture system using SGC‐7901 as the model. Silibinin treatment could inhibit the cell growth and cause a prominent G2 phase arrest and apoptosis in dose‐ and time‐dependent manner. In mechanistic studies, Silibinin decreased the protein level of p34cdc2, which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC‐7901 cells. In addition, Silibinin caused an increase in p53 and p21 protein level as well as mRNA levels. Interestingly, Silibinin‐induced apoptosis in SGC‐7901 cells was independent of caspases activation. These results indicated that Silibinin is a cell‐cycle regulator and apoptosis inducer in human gastric carcinoma SGC‐7901 cells and might be used as a candidate chemopreventive agent for gastric carcinoma prevention and intervention. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

9.
Sinomenine (SIN) is an isoquinoline derived from Caulis Sinomenii that has been used to treat rheumatoid arthritis and osteoarthritis for several decades in China. This study aims to reveal the effects of SIN on mouse chondrogenic ATDC5 cells growth and inflammation. SIN was used to treat ATDC5 cells injured by lipopolysaccharides (LPS). The following parameters were determined for evaluating the treatment effects of SIN: cell viability, apoptosis, reactive oxygen species generation, and pro‐inflammatory cytokines release. Besides, the expression of LPS‐sensitive miRNA (miR‐192) and the activation of NF‐κB and MAPK signaling were studied to explain SIN's function. SIN with concentration of 30 μM significantly attenuated LPS‐induced cell damage via increasing cell viability, inhibiting apoptosis and reactive oxygen species generation, and declining IL‐6 and TNF‐α release. miR‐192 was downregulated by SIN treatment. Restoration of miR‐192 expression by miRNA transfection could significantly impede SIN's protective action. Besides, the inhibitory effects of SIN on the activation of NF‐κB and MAPK signaling were attenuated by miR‐192 overexpression. Furthermore, GDF11 was found to be a target gene of miR‐192. LPS‐mediated injury to chondrogenic ATDC5 cells can be relieved by SIN via downregulating miR‐192 and subsequently repressing the activation of NF‐κB and MAPK signaling.  相似文献   

10.
11.
Costunolide, a sesquiterpene lactone, is a biologically active molecule found in most of the medicinally valuable plants. The present study aims to evaluate the anticancer property of costunolide isolated from Costus speciosus against breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Costunolide effectively reduced the viability of both MCF‐7 and MDA‐MB‐231 cell lines at an IC50 value of 40 μM. Flow cytometric analysis revealed costunolide mediated cell cycle arrest at G2/M phase in both the cell types. Western blotting results confirmed the alterations in the expression of cell cycle regulators (cyclin D1, D3, CDK‐4, CDK‐6, p18 INK4c, p21 CIP1/Waf‐1 and p27 KIP1) and apoptosis inducers (caspase‐3 and caspase‐9) upon costunolide treatment in comparison with their expressions in normal breast cell line (MCF‐10A). Costunolide mediated downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators were related to the induction of apoptosis in cancer cells. The above results were validated with in‐silico results that predicted stable interactions between costunolide and cancer targets. Thus costunolide effectively induced breast cancer cell apoptosis targeting cell cycle regulation, and the compound can be used as an effective herbal therapeutic molecule to treat breast cancer with further explorations. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

12.
13.
Ganoderic Acid A (GAA) is often applied for healing cardiovascular and cerebrovascular ailments, but the influences in cerebral ischemia injury are still hazy. The research delved into the functions of GAA in hypoxia‐triggered impairment in PC12 cells. PC12 cells received hypoxia management for 12 hr, and subsequently, cell viability, migration, apoptosis, and correlative protein levels were assessed. After preprocessing with GAA, above cell behaviors were monitored again. The vector of microRNA (miR)‐153 inhibitor was utilized for PC12 cell transfection to further explore the functions of miR‐153 in hypoxia‐impaired cells. Pathways of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were investigated via executing western blot for uncovering the latent mechanism. Results revealed that hypoxia disposition triggered PC12 cells impairment via restraining cell viability and migration and accelerating apoptosis. However, GAA visibly mollified hypoxia‐provoked impairment in PC12 cells. Interestingly, the enhancement of miR‐153 triggered by GAA was observed in hypoxia‐impaired PC12 cells. After miR‐153 inhibitor transfection, the protective functions of GAA in hypoxia‐impaired PC12 cells were dramatically inversed. Furthermore, GAA caused PI3K/AKT and mTOR activations via enhancement of miR‐153 in hypoxia‐impaired PC12 cells. The findings evinced that GAA exhibited the protective functions in PC12 cells against hypoxia‐evoked impairment through activating PI3K/AKT and mTOR via elevating miR‐153.  相似文献   

14.
15.
Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA‐21 (miR‐21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up‐regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR‐21 overexpression (p < .05 or p < .01). On the other side, miR‐21 silence showed contrary results (p < .05) as relative to miR‐21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down‐regulating miR‐21.  相似文献   

16.
Dihydroxy‐isosteviol methyl ester (DIME), the principal biological compound isolated from the medicinal plant Pulsatilla nigricans (Fam: Ranunculaceae) having the molecular formula of C21H34O3 (molecular weight 334.25), was administered to cervical cancer cells (HeLa) in vitro to evaluate its possible apoptotic (anti‐cancer) potentials. We analyzed the expression of p53, Bax, Bcl2, Apaf and caspase 3 signal proteins and analyzed the early apoptotic events in HeLa cells induced by DIME using protocols like Annexin V‐FITC and PI staining. DIME caused a significant decrease in cell viability, induced nuclear condensation and inter‐nucleosomal DNA fragmentation. We further studied the interaction of DIME with calf thymus DNA as target through circular‐dichroism spectra. Results showed that DIME interacted with DNA, bringing indiscernible changes in structure and conformation. Thus, DIME showed its capability to induce apoptosis in cancer cells, signifying its utility in drug design as a possible candidate for chemoprevention. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

17.
Decreasing numbers, and impaired function, of pancreatic β‐cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic β‐cells against glucotoxicity‐induced apoptosis using a rat insulinoma cell line (INS‐1). High glucose treatment (30 mM) induced INS‐1 cell death; however, the level of glucose‐induced apoptosis was significantly reduced in cells treated with 100‐μM phloroglucinol. Treatment with 10–100‐μM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose‐dependently in INS‐1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti‐apoptotic Bcl‐2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose‐induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic β‐cells against glucose‐induced apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

18.
Curcumin (CUR) is a kind of polyphenolic compound and widely used in the treatment of diseases. However, the involvement of CUR in thymic carcinoma remains unknown. The object of our research is to clarify the role of CUR and related regulatory mechanism in thymic carcinoma cells. After treatment with CUR for 24 hr, cell viability, apoptosis, migration, and invasion of TC1889 cells were measured. Real‐time polymerase chain reaction was executed to examine the expression of microRNA‐27a (miR‐27a) in thymic carcinoma tissues and TC1889 cells. After miR‐27a mimic transfection, whether miR‐27a is involved in CUR‐modulated cell behaviors was measured. Finally, western blot was utilized to detect mTOR and Notch 1 pathways‐linked proteins. CUR restrained cell viability and increased cell apoptosis of TC1889 cells. In addition, cell migration and invasion were restrained by CUR. Meanwhile, miR‐27a expression was positively regulated in thymic carcinoma tissues and downregulated by CUR in TC1889 cells. Overexpressed miR‐27a reversed the CUR‐induced reduction of growth, migration, and invasion in TC1889 cells. Furthermore, CUR blocked mTOR and Notch 1 pathways via downregulating miR‐27a. We demonstrated that CUR blocked mTOR and Notch 1 pathways via downregulating miR‐27a, thereby suppressing cell growth, migration, and invasion of thymic carcinoma cells.  相似文献   

19.
Myocarditis is a common heart disease which lacks effective treatment till now. Baicalin possesses plenty of activities, including anti‐inflammation. In this investigation, we attempted to investigate the influences of Baicalin on Lipopolysaccharide (LPS)‐evoked H9c2 cells.Cells viability, apoptosis, and expressions of apoptosis‐associated proteins were, respectively, measured utilizing CCK‐8 assay, flow cytometry and western blot. The levels of IL‐6 and TNF‐α were detected through enzyme‐linked immunosorbent assay, western blot and qRT‐PCR. miR‐21 expression was detected through qRT‐PCR and was silenced using cell transfection. The expressions of NF‐κB and PDCD4/JNK pathways related proteins were measured through western blot. We found that LPS stimulation induced cell apoptosis and upregulation of IL‐6 and TNF‐α. Baicalin treatment effectively suppressed LPS‐induced inflammation and apoptosis. The NF‐κB and PDCD4/JNK pathways were blocked by Baicalin. Additionally, the enhanced expression of miR‐21 triggered by LPS was further elevated by Baicalin. Further study revealed that the inhibiting effects of Baicalin on LPS‐evoked injury were largely attenuated by knockdown of miR‐21. Moreover, the associated NF‐κB and JNK pathways, which were suppressed by Baicalin treatment, were then activated by knockdown of miR‐21. Our present study revealed that Baicalin alleviated LPS‐evoked inflammatory injury via suppressing the NF‐κB and PDCD4/JNK pathways through regulating miR‐21 expression.  相似文献   

20.
Recent evidence suggests that polyphenolic compounds from plants have anti‐invasion and anti‐metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti‐metastatic effects of pKAL on the highly metastatic MDA‐MB‐231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial‐mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA‐MB‐231 cells in a dose‐dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA‐MB‐231 cells to ECs through reducing vascular cell adhesion molecule‐1 expression of MDA‐MB‐231 and ECs, but not intracellular adhesion molecule‐1 at the concentrations where pKAL did not influence the cell viability of either MDA‐MB‐231 cells nor EC. Further, pKAL inhibited tumor necrosis factor‐activated MDA‐MB‐231 breast cancer cell invasion through inhibition of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule‐1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

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