scholarly journals The Effect of Compound Sophora on Fluorouracil and Oxaliplatin Resistance in Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
WeiHua Yin ◽  
GuPing Zhong ◽  
HuiZhen Fan ◽  
HongMei Xia
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Sw480 Cell ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Chemotherapy Drugs ◽  
Protein Levels ◽  
Enhanced Expression

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P<0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P<0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

scholarly journals Exosomal Micro RNA-107 Reverses Chemotherapeutic Drug Resistance of Gastric Cancer Cells Through HMGA2/mTOR/P-gp Pathway

2021 ◽  
Author(s):  
Lu Jiang ◽  
Yan Zhang ◽  
Linghui Guo ◽  
Chaoyang Liu ◽  
Weihong Ren
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Chemotherapy Drug ◽  
Chemotherapy Drugs

Abstract Background: RNA cargo in exosomes，especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse theresistance of gastric cancer cells to the chemotherapy drugs. Methods: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins were detected by western blot. Results: Our results indicated that the isolated exosomes were demostrated typically cup-like lipid bilayer membrans structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (DDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant gastric cells to the chemotherapeutic drugs,which was verificated by exosomal inhibitor GW4896. Mechanistically, the reversal effect were mainly mediated by exosome-secreted miR-107 through downregulating the expression of targert molecular HMGA2, and inhibiting HMGA2/mTOR/P-gp pathway, which were proofed by luciferase reporter assay and rescue assay. Conclusions: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and appling exosomal miR-107 may be a novel target in gastric cancers treatment.

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 Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1820
Author(s):  
Chengcheng Hao ◽  
Yuxin Cui ◽  
Jane Lane ◽  
Shuqin Jia ◽  
Jiafu Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Prognostic Value ◽  
Splice Variants ◽  
Tnm Staging ◽  
Migration And Invasion ◽  
Ros Production ◽  
Gastric Cancer Cells ◽  
Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

scholarly journals Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4417
Author(s):  
Rabin Neupane ◽  
Saloni Malla ◽  
Mariam Sami Abou-Dahech ◽  
Swapnaa Balaji ◽  
Shikha Kumari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colon Cancer Cells ◽  
Apoptotic Pathway ◽  
Anticancer Efficacy ◽  
Colon Cell ◽  
Ic50 Values ◽  
Induced Apoptosis

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

scholarly journals Anticancer effects of bifidobacteria on colon cancer cell lines

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeinab Faghfoori ◽  
Mohammad Hasan Faghfoori ◽  
Amir Saber ◽  
Azimeh Izadi ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Rt Pcr ◽  
Anticancer Effects ◽  
Colon Cancer Cell Lines ◽  
Apoptotic Genes

Abstract Background Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. Methods The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. Results The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. Conclusions In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

scholarly journals Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Fangfang Yong ◽  
Hemei Wang ◽  
Chao Li ◽  
Huiqun Jia
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Forkhead Box ◽  
Induced Apoptosis

Objective Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. Methods GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. Results FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. Conclusions Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.

Action of a library of O-glycosylation inhibitors on the growth of human colorectal cancer cells in culture

2005 ◽  
Vol 33 (4) ◽  
pp. 721-723 ◽  
Author(s):  
G. Patsos ◽  
V. Hebbe-Viton ◽  
R. San Martin ◽  
C. Paraskeva ◽  
T. Gallagher ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Growth Patterns ◽  
Limited Information ◽  
Human Colorectal Cancer ◽  
Human Colorectal Cancer Cell ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Cell Lines

O-glycosylation is thought to play a significant role in the regulation of cell growth. However, only limited information is available, and few specific and selective inhibitors have been found. We have synthesized a library of O-glycosylation inhibitors based on benzyl-O-N-acetyl-D-galactosamine. These inhibitors were tested with an established series of human colorectal cancer cell lines, which model the adenoma-carcinoma sequence. Cancer cells were incubated with the inhibitors, and examined for cell growth patterns, and cellular and subcellular glycosylation using a range of lectins with confocal microscopy. The specificity of O-glycan inhibition was confirmed for the library, relative to other forms of glycosylation. All inhibitors tested resulted in smaller cell yields. However, a differential effect on O-glycosylation was detected using the lectins showing variation of localization at a subcellular level in the various cell lines. Further differential action of the inhibitor library was observed for apoptosis and on the cell cycle with the cell lines tested. This work demonstrates that O-glycosylation is closely involved in the regulation of cell growth in colorectal cancer cells and that the generation of a library of low-molecular-mass inhibitors offers a valuable means of examining this regulation at the molecular level.

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