scholarly journals hCAIX Expression and Cell Cycle in Cytokine Stimulated Human Colon Cancer Cells

2019 ◽  
Author(s):  
Rahsan Ilikci Sagkan ◽  
Feray Kockar ◽  
Ali Sengul ◽  
Sukran Yilmaz ◽  
Ugur Musabak

Abstract Background: At the aim of this study, we investigated the effects of different kind of cytokines and the combinations of which on human carbonic anhydrase IX ( hCAIX) expression in HT-29 cell selected as colon carcinoma model for different doses and time of exposure to determine role of cytokines for treatment of colon carcinoma cells. Results: To sum up, h CA9 expression in the levels of gene and protein increased in HT-29 cells when stimulated with 1000 U/mL TGF-β for 24 h. The stimulation of HT-29 cells with IL1 α alone and IL1α- TGF-β combination has not revealed any effect on hCA9 expression in both levels of gene and protein in contrast to, 1000 U/mL IL1α-TNFα and especially TGFβ-TNFα have reducing effect on h CA9 expression level in HT-29 cells for time ranges of 24 h, 48 h, 72 h. In addition to this data, it was observed that HT-29 cells at the phase of G0G1 are arrested in cell cycle when stimulated with either of 1000 U/mL IL1α-TNFα and TGFβ-TNFα. Moreover, it was observed that h CA9 expression level in HT-29 cells decreases at the phases of synthesis (S) and G2M. Discussion: We concluded that combination of TNFα-TGFβ has created antagonistic effect on hCA9 expression in HT-29 colon cancer cell model. On the other hand, combination of TNFα-IL1α caused sinergistic effect on h CA9 expression level in this cell model. When these results are demonstrated decrease in the cytokine exposed hCA9 expression is a finding to develop a novel approach for anticancer therapy. Conclusion: Our finding related to the change in the expression of hCA9 following cytokine stimulate to colon cancer cell line gives an idea about the effect of cytokine stimulation on the expression of this gene which will be a hot spot research in colon carcinogenesis. Methods: HT-29 colon cells were chosen as a colorectal adenocarcinoma model. hCA9 gene expression in the level of mRNA was measured in cytokines stimulated HT-29 cells by Quantitative Real-time PCR. Meanwhile, hCAIX expression in the level of protein and cell cycle aassay were detected by flow cytometry.

2021 ◽  
Author(s):  
Jakeb SSM Petersen ◽  
Sarah Baird

Abstract Purpose: Anti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infestations. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies. We compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. Methods: The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer) and mesenchymal stem cells, using the MTT assay. Their effects on the cell cycle, tubulin levels and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy. Results: Mebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 hours. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted.Conclusion: Mebendazole and albendazole cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, which involves the destabilisation of microtubules.


2019 ◽  
Vol 9 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Ibrahim Awad Mohammed ◽  
Muhammad Nadeem Akhtar ◽  
Foo Jhi Biau ◽  
Yin Sim Tor ◽  
Seema Zareen ◽  
...  

<P>Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. </P><P> Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. </P><P> Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. </P><P> Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62&#177;0.61 and 4.44&#177;0.66 &#181;g/mL) and pinostrobin chalcone (2), (IC50 = 20.42&#177;2.23 and 22.51&#177;0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. </P><P> Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.</P>


2007 ◽  
Vol 43 (2) ◽  
pp. 195-205 ◽  
Author(s):  
Ana García-Navarro ◽  
Cristina González-Puga ◽  
Germaine Escames ◽  
Luis C. López ◽  
Ana López ◽  
...  

2016 ◽  
Vol 16 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Ji-Ye Kee ◽  
Yo-Han Han ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Jeong-Geon Mun ◽  
...  

Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.


Molbank ◽  
10.3390/m1173 ◽  
2020 ◽  
Vol 2020 (4) ◽  
pp. M1173
Author(s):  
Rajaiah Raveesha ◽  
Malavalli Guruswamy Dileep Kumar ◽  
Salekoppal Boregowda Benaka Prasad

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.


2003 ◽  
Vol 46 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Ji Yeon Kim ◽  
Hee Jong Woo ◽  
Young-Suk Kim ◽  
Kyoung Heon Kim ◽  
Hyong Joo Lee

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