• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.427-432
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• 2014

Isocitrate dehydrogenase (IDH) is of great importance in cell metabolism and energy conversion. IDH mutation in glioma cells is reported to be associated with an increased overall survival. However, effects biological behavior of therapy of gliomas are unclear. Here, we investigated the influence of wild-type and mutated IDH genes on glioma cell biological behavior and response to chemotherapy. Relevant mechanisms were further explored. We designed our study on the background of the IDHR132H mutation. Stable cell lines were constructed by transfection. The CCK-8 method was used to assess cell proliferation, flow cytometry for the cell cycle and cell apoptosis, and the transwell method for cell invasion. Nude mouse models were employed to determine tumorigenesis and sensitivity to chemotherapy. Western blotting was used to detect relevant protein expression levels. We found that overexpression of wild IDH1 gene did not cause changes in the cell cycle, apoptosis and invasion ability. However, it resulted in chemotherapy resistance to a high dose of temozolomide (TMZ) in vivo and in vitro. The IDH1 mutation caused cell cycle arrest in G1 stage and a reduction of proliferation and invasion ability, while raising sensitivity to chemotherapy. This may provide an explanation for the better prognosis of IDH1 mutated glioma patients and the relative worse prognosis of their wild-type IDH1 counterparts. We also expect IDH1 mutations may be optimized as new targets to improve the prognosis of glioma patients.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.494-502
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• 2018

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1041-1048
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• 2018

Purpose: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. Materials and Methods: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. Results: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). Conclusion: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

• Journal of Microbiology and Biotechnology
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• 제32권7호
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• pp.938-948
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• 2022

Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.

• 한국자원식물학회지
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• 제36권3호
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• pp.207-218
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• 2023

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.159-165
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• 2012

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.

• Clinical and Experimental Pediatrics
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• 제48권7호
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• pp.691-695
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• 2005

There is scientific evidence that administration of probiotics is effective in the treatment of acute infectious diarrhea in children and the prevention of antibiotic associated diarrhea and nosocomial/community acquired diarrhea. Probiotics prevent relapse of recurrent pouchitis and decrease the initial onset of pouchitis in ulcerative colitis. Probiotic organisms suppress growth of pathogens as well as their epithelial attachment and/or invasion either directly by secreting antimicrobial substances or by stimulating host expression of protective molecules. Additionally, probiotics enhance mucosal barrier function and can stimulate host production of immunosuppressive molecules that downregulate inflammatory responses or allergic immune response. Mechanisms of action explain therapeutic effects and randomized controlled trials are warranted before recommendations for therapeutic or preventive use can be given.

• BMB Reports
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• 제44권7호
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• pp.423-434
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• 2011

A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

• BMB Reports
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• 제56권4호
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• pp.216-224
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• 2023

Centrosome abnormalities are hallmarks of human cancers. Structural and numerical centrosome abnormalities correlate with tumor aggressiveness and poor prognosis, implicating that centrosome abnormalities could be a cause of tumorigenesis. Since Boveri made his pioneering recognition of the potential causal link between centrosome abnormalities and cancer more than a century ago, there has been significant progress in the field. Here, we review recent advances in the understanding of the causes and consequences of centrosome abnormalities and their connection to cancers. Centrosome abnormalities can drive the initiation and progression of cancers in multiple ways. For example, they can generate chromosome instability through abnormal mitosis, accelerating cancer genome evolution. Remarkably, it is becoming clear that the mechanisms by which centrosome abnormalities promote several steps of tumorigenesis are far beyond what Boveri had initially envisioned. We highlight various cancer-promoting mechanisms exerted by cells with centrosome abnormalities and how these cells possessing oncogenic potential can be monitored.

• Journal of Korean Neurosurgical Society
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• 제51권3호
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• pp.147-150
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• 2012

Glioblastoma multiforme(GBM) is the most aggressive intracranial tumor and it commonly spreads by direct extension and infiltration into the adjacent brain tissue and along the white matter tract. The metastatic spread of GBM outside of the central nervous system (CNS) is rare. The possible mechanisms of extraneural metastasis of the GBM have been suggested. They include the lymphatic spread, the venous invasion and the direct invasion through dura and bone. We experienced a 46-year-old man who had extraneural metastasis of the G8M on his left neck. The patient was treated with surgery for 5 times, radiotherapy and chemotherapy. He had survived 6 years since first diagnosed. Although the exact mechanism of the extraneural metastasis is not well understood, this present case shows the possibility of extraneural metastasis of the G8M, especially in patients with long survival.