scholarly journals Schlafen-3 decreases cancer stem cell marker expression and autocrine/juxtacrine signaling in FOLFOX-resistant colon cancer cells

2011 ◽  
Vol 301 (2) ◽  
pp. G347-G355 ◽  
Author(s):  
Phil-Sun Oh ◽  
Vaishali B. Patel ◽  
Matthew A. Sanders ◽  
Shailender S. Kanwar ◽  
Yingjie Yu ◽  
...  

We have previously demonstrated that expression of the novel gene schlafen-3 (Slfn-3) correlates with intestinal epithelial cell differentiation (Patel VB, Yu Y, Das JK, Patel BB, Majumdar AP. Biochem Biophys Res Commun 388: 752–756, 2009). The present investigation was undertaken to examine whether Slfn-3 plays a role in regulating differentiation of FOLFOX-resistant (5-fluorouracil + oxaliplatin) colon cancer cells that are highly enriched in cancer stem cells (CSCs). Transfection of Slfn-3 in FOLFOX-resistant colon cancer HCT-116 cells resulted in increase of alkaline phosphatase activity, a marker of intestinal differentiation. Additionally, Slfn-3 transfection resulted in reduction of mRNA and protein levels of the CSC markers CD44, CD133, CD166, and aldehyde dehydrogenase 1 in both FOLFOX-resistant HCT-116 and HT-29 cells. This was accompanied by decreased formation of tumorosphere/colonosphere (an in vitro model of tumor growth) in stem cell medium and inhibition of expression of the chemotherapeutic drug transporter protein ABCG2. Additionally, Slfn-3 transfection of FOLFOX-resistant HCT-116 and HT-29 cells reduced Hoechst 33342 dye exclusion. Finally, Slfn-3 transfection inhibited the expression of transforming growth factor-α in both FOLFOX-resistant colon cancer cells, but stimulated apoptosis in response to additional FOLFOX treatment. In summary, our data demonstrate that Slfn-3 expression inhibits multiple characteristics of CSC-enriched, FOLFOX-resistant colon cancer cells, including induction of differentiation and reduction in tumorosphere/colonosphere formation, drug transporter activity, and autocrine stimulation of proliferation. Thus Slfn-3 expression may render colon CSCs more susceptible to cancer chemotherapeutics.

2021 ◽  
Vol 10 (1) ◽  
pp. 572-585
Author(s):  
Darren Yi Sern Low ◽  
Camille Keisha Mahendra ◽  
Janarthanan Supramaniam ◽  
Loh Teng Hern Tan ◽  
Learn Han Lee ◽  
...  

Abstract In this study, ultrasonically driven biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Swietenia macrophylla seed ethyl acetate fraction (SMEAF) has been reported. X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the presence of a pure hexagonal wurtzite structure of ZnO. Field emission scanning electron microscope images revealed the formation of uniquely identifiable uniform rice-shaped biologically synthesized ZnOSMEAF particles. The particle sizes of the biosynthesized NPs ranged from 262 to 311 nm. The underlying mechanisms for the biosynthesis of ZnOSMEAF under ultrasound have been proposed based on FTIR and XRD results. The anticancer activity of the as-prepared ZnOSMEAF was investigated against HCT-116 human colon cancer cell lines via methyl thiazolyl tetrazolium assay. ZnOSMEAF exhibited significant anticancer activity against colon cancer cells with higher potency than ZnO particles prepared using the chemical method and SMEAF alone. Exposure of HCT-116 colon cancer cells to ZnOSMEAF promoted a remarkable reduction in cell viability in all the tested concentrations. This study suggests that green sonochemically induced ZnO NPs using medicinal plant extract could be a potential anticancer agent for biomedical applications.


2016 ◽  
Vol 65 (31) ◽  
pp. 6477-6487 ◽  
Author(s):  
María-Carmen López de las Hazas ◽  
Juana I. Mosele ◽  
Alba Macià ◽  
Iziar A. Ludwig ◽  
María-José Motilva

2010 ◽  
Author(s):  
Lloyd F. Alfonso ◽  
Raghavender Chivukula ◽  
Srinivasan Marimuthu ◽  
Jayarama B. Gunaje

2012 ◽  
Vol 5 (1) ◽  
pp. 305-310 ◽  
Author(s):  
SE-MI OH ◽  
JINHEE KIM ◽  
JUN LEE ◽  
JIN-MU YI ◽  
DAL-SEOK OH ◽  
...  

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Tomasz Przybyła ◽  
Monika Sakowicz-Burkiewicz ◽  
Izabela Maciejewska ◽  
Hanna Bielarczyk ◽  
Tadeusz Pawełczyk

Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is an ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1 showed altered expression of epithelial and mesenchymal markers and exhibited increased proliferation rate compared to the parental cells. HCT-116 cells with suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29 cells. Silencing ID1 resulted in altered expression of genes encoding enzymes metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA level for thymidine phosphorylase, uridine-cytydine kinase 2 and dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an increase of mRNA level for thymidine phosphorylase, thymidyne kinase and uridine-cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and thymidylate synthetase mRNA levels. In conclusion ID1 expression impacts the sensitivity of colon cancer cells to 5-FU and may be considered as potential predictive marker in CRC treatment.


2014 ◽  
Vol 156 ◽  
pp. 277-289 ◽  
Author(s):  
Soheil Zorofchian Moghadamtousi ◽  
Hamed Karimian ◽  
Elham Rouhollahi ◽  
Mohammadjavad Paydar ◽  
Mehran Fadaeinasab ◽  
...  

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