scholarly journals TMEM106C is overexpressed and modulates cell mobility in metastatic colon cancer cells

2021 ◽  
Author(s):  
Muzaffer DÜKEL
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Cell Mobility

scholarly journals Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1261
Author(s):  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Elyani Mohamad ◽  
Swee Keong Yeap ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Curcuma Longa ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

scholarly journals Deacetylase Plus Bromodomain Inhibition Downregulates ERCC2 and Suppresses the Growth of Metastatic Colon Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1438
Author(s):  
Sabeeta Kapoor ◽  
Trace Gustafson ◽  
Mutian Zhang ◽  
Ying-Shiuan Chen ◽  
Jia Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Excision Repair ◽  
Critical Role ◽  
Rat Colon ◽  
Precision Oncology ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Combination Drug ◽  
Human Colon Cancer

There is growing evidence that DNA repair factors have clinical value for cancer treatment. Nucleotide excision repair (NER) proteins, including excision repair cross-complementation group 2 (ERCC2), play a critical role in maintaining genome integrity. Here, we examined ERCC2 expression following epigenetic combination drug treatment. Attention was drawn to ERCC2 for three reasons. First, from online databases, colorectal cancer (CRC) patients exhibited significantly reduced survival when ERCC2 was overexpressed in colon tumors. Second, ERCC2 was the most highly downregulated RNA transcript in human colon cancer cells and rat tumors after treatment with the histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) plus JQ1, which is an inhibitor of the bromodomain and extraterminal domain (BET) family. Third, as reported here, RNA-sequencing of polyposis in rat colon (Pirc) polyps following treatment of rats with JQ1 plus 6-methylsulfinylhexyl isothiocyanate (6-SFN) identified Ercc2 as the most highly downregulated gene. The current work also defined promising second-generation epigenetic drug combinations with enhanced synergy and efficacy, especially in metastasis-lineage colon cancer cells cultured as 3D spheroids and xenografts. This investigation adds to the growing interest in combination approaches that target epigenetic ‘readers’, ‘writers’, and ‘erasers’ that are deregulated in cancer and other pathologies, providing new avenues for precision oncology and cancer interception.

Modification of Gene Products Involved in Resistance to Apoptosis in Metastatic Colon Cancer Cells: Roles of Fas, Apaf-1, NFκB, IAPs, Smac/DIABLO, and AIF

2007 ◽  
Vol 142 (1) ◽  
pp. 184-194 ◽  
Author(s):  
Sergio Huerta ◽  
John H. Heinzerling ◽  
Yu-Mei Anguiano-Hernandez ◽  
Sara Huerta-Yepez ◽  
Jeffrey Lin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Metastatic Colon Cancer ◽  
Gene Products ◽  
Colon Cancer Cells

scholarly journals Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis

2020 ◽  
Vol 21 (20) ◽  
pp. 7469 ◽  
Author(s):  
Jin Hong Lim ◽  
Kyung Hwa Choi ◽  
Soo Young Kim ◽  
Cheong Soo Park ◽  
Seok-Mo Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Drug Effects ◽  
Control Group ◽  
Metastatic Colon Cancer ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.

Detection of metastatic colon cancer cells in sentinel nodes by flow cytometry

2008 ◽  
Vol 334 (1-2) ◽  
pp. 122-133 ◽  
Author(s):  
Mona Karlsson ◽  
Olle Nilsson ◽  
Magnus Thörn ◽  
Ola Winqvist
Keyword(s):  
Colon Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Sentinel Nodes

scholarly journals Expression of Kinase-defective Mutants of c-Src in Human Metastatic Colon Cancer Cells Decreases Bcl-xLand Increases Oxaliplatin- and Fas-induced Apoptosis

2004 ◽  
Vol 279 (44) ◽  
pp. 46113-46121 ◽  
Author(s):  
Gareth J. Griffiths ◽  
Mei Yee Koh ◽  
Valerie G. Brunton ◽  
Christopher Cawthorne ◽  
Natalie A. Reeves ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Vector Control ◽  
Cancer Cells ◽  
Kinase Activity ◽  
Src Kinase ◽  
Human Colon ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Induced Apoptosis

Tumor resistance to current drugs prevents curative treatment of human colon cancer. A pressing need for effective, tumor-specific chemotherapies exists. The non-receptor-tyrosine kinase c-Src is overexpressed in >70% of human colon cancers and represents a tractable drug target. KM12L4A human metastatic colon cancer cells were stably transfected with two distinct kinase-defective mutants ofc-src.Their response to oxaliplatin, to SN38, the active metabolite of irinotecan (drugs active in colon cancer), and to activation of the death receptor Fas was compared with vector control cells in terms of cell cycle arrest and apoptosis. Both kinase-defective forms of c-Src co-sensitized cells to apoptosis induced by oxaliplatin and Fas activation but not by SN38. Cells harboring kinase-defective forms of c-Src carrying function blocking point mutations in SH3 or SH2 domains were similarly sensitive to oxaliplatin, suggesting that reduction in kinase activity and not a Src SH2-SH3 scaffold function was responsible for the observed altered sensitivity. Oxaliplatin-induced apoptosis, potentiated by kinase-defective c-Src mutants, was dependent on activation of caspase 8 and associated with Bid cleavage. Each of the stable cell lines in which kinase-defective mutants of c-Src were expressed had reduced levels of Bcl-xL.However, inhibition of c-Src kinase activity by PP2 in vector control cells did not alter the oxaliplatin response over 72 h nor did it reduce Bcl-xLlevels. The data suggest that longer term suppression of Src kinase activity may be required to lower Bcl-xLlevels and sensitize colon cancer cells to oxaliplatin-induced apoptosis.

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