The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro

2017 ◽  
Vol 91 (10) ◽  
pp. 3365-3372 ◽  
Author(s):  
Afshin Mohammadi-Bardbori ◽  
Farzaneh Bastan ◽  
Amin-Reza Akbarizadeh
Keyword(s):  
Cell Growth ◽  
Functional Roles ◽  
Bioactive Molecule ◽  
Signal Substance

A natural product phillygenin suppresses osteosarcoma growth and metastasis by regulating the SHP-1/JAK2/STAT3 signaling

2021 ◽  
Vol 85 (2) ◽  
pp. 307-314
Author(s):  
Xiaomin Ding ◽  
Danqing Lu ◽  
Jianbo Fan
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Janus Kinase ◽  
Potential Candidate ◽  
Osteosarcoma Cell ◽  
Cancer Cell Growth ◽  
Functional Roles ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

ABSTRACT Osteosarcoma represents one of the most devastating cancers due to its high metastatic potency and fatality. Osteosarcoma is insensitive to traditional chemotherapy. Identification of a small molecule that blocks osteosarcoma progression has been a challenge in drug development. Phillygenin, a plant-derived tetrahydrofurofuran lignin, has shown to suppress cancer cell growth and inflammatory response. However, how phillygenin plays functional roles in osteosarcoma has remained unveiled. In this study, we showed that phillygenin inhibited osteosarcoma cell growth and motility in vitro. Further mechanistic studies indicated that phillygenin blocked STAT3 signaling pathway. Phillygenin led to significant downregulation of Janus kinase 2 and upregulation of Src homology region 2 domain-containing phosphatase 1. Gene products of STAT3 regulating cell survival and invasion were also inhibited by phillygenin. Therefore, our studies provided the first evidence that phillygenin repressed osteosarcoma progression by interfering STAT3 signaling pathway. Phillygenin is a potential candidate in osteosarcoma therapy.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

Anticancer Potential of Aguerin B, a Sesquiterpene Lactone Isolated from Centaurea behen in Metastatic Breast Cancer Cells

2020 ◽  
Vol 15 (2) ◽  
pp. 165-173
Author(s):  
Elaheh Amini ◽  
Mohammad Nabiuni ◽  
Seyed Bahram Behzad ◽  
Danial Seyfi ◽  
Farhad Eisvand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Sesquiterpene Lactone ◽  
Sesquiterpene Lactones ◽  
Metastatic Breast ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Skin Malignancy

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide. Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α). Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR. Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels. Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

Survival and Function of Fibroblasts Stored as Stock Cultures at a Non-freezing Temperature

1993 ◽  
Vol 21 (2) ◽  
pp. 206-209
Author(s):  
Anders H. G. Andrén ◽  
Anders P. Wieslander
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Freezing Temperature ◽  
Mouse Fibroblast ◽  
Toxic Response ◽  
Normal Manner ◽  
And Function

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.

scholarly journals Silencing of Vangl2 attenuates the inflammation promoted by Wnt5a via MAPK and NF-κB pathway in chondrocytes

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ke Zhang ◽  
Zhuoying Li ◽  
Yunyang Lu ◽  
Linyi Xiang ◽  
Jiadong Sun ◽  
...  
Keyword(s):  
Western Blotting ◽  
Planar Cell Polarity ◽  
Type Ii Collagen ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Microenvironment ◽  
Functional Roles ◽  
Protein Levels ◽  
Oa Chondrocytes

Abstract Background The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes. Methods Chondrocytes were treated with IL-1β (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then, the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. Results IL-1β induced the production of Vangl2, Wnt5a, and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13, and IL-6 at both gene and protein levels and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes. Conclusions For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.

scholarly journals Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3046
Author(s):  
Ming-Huei Chou ◽  
Hui-Ching Chuang ◽  
Yu-Tsai Lin ◽  
Ming-Hsien Tsai ◽  
Ying-Hsien Kao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hnscc Cell ◽  
Proliferation And Migration

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

scholarly journals HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Lei ◽  
Wen-Ting Yang ◽  
Peng-Sheng Zheng
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Tumor Formation ◽  
Cervical Cancer Cell ◽  
Cancer Cell Growth ◽  
Bioinformatics Analyses

AbstractHomeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.

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