scholarly journals Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1225 ◽  
Author(s):  
Qing Ren ◽  
Bo Yang ◽  
Guangzhen Zhu ◽  
Shunyu Wang ◽  
Chengli Fu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Lactobacillus Plantarum ◽  
Linolenic Acid ◽  
Probiotic Bacterium ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Concentration Dependent Manner ◽  
Caspase 1 ◽  
Parp 1

Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon cancer cells were proved.

scholarly journals Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells

2020 ◽  
Author(s):  
Qing Ren ◽  
Bo Yang ◽  
Guangzhen Zhu ◽  
Shunyu Wang ◽  
Chengli Fu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Lactobacillus Plantarum ◽  
Linolenic Acid ◽  
Antioxidant Defenses ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Alpha Linolenic Acid ◽  
Concentration Dependent Manner ◽  
Caspase 1

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.

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 Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongxiao Jiang ◽  
Shufei Ding ◽  
Zhujun Mao ◽  
Liyan You ◽  
Yeping Ruan
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Time Dependent ◽  
Integrated Analysis ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Dapi Staining ◽  
Aloe Emodin

Abstract Background Colon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic. Methods We identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells. Results The MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria. Conclusion These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

scholarly journals Transforming Growth Factor β Mediates Drug Resistance by Regulating the Expression of Pyruvate Dehydrogenase Kinase 4 in Colorectal Cancer

2016 ◽  
Vol 291 (33) ◽  
pp. 17405-17416 ◽  
Author(s):  
Yang Zhang ◽  
Yi Zhang ◽  
Liying Geng ◽  
Haowei Yi ◽  
Wei Huo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Mouse Xenograft Model

Drug resistance is one of the main causes of colon cancer recurrence. However, our understanding of the underlying mechanisms and availability of therapeutic options remains limited. Here we show that expression of pyruvate dehydrogenase kinase 4 (PDK4) is positively correlated with drug resistance of colon cancer cells and induced by 5-fluorouracil (5-FU) treatment in drug-resistant but not drug-sensitive cells. Knockdown of PDK4 expression sensitizes colon cancer cells to 5-FU or oxaliplatin-induced apoptosis in vitro and increases the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. In addition, we demonstrate for the first time that TGFβ mediates drug resistance by regulating PDK4 expression and that 5-FU induces PDK4 expression in a TGFβ signaling-dependent manner. Mechanistically, knockdown or inhibition of PDK4 significantly increases the inhibitory effect of 5-FU on expression of the anti-apoptotic factors Bcl-2 and survivin. Importantly, studies of patient samples indicate that expression of PDK4 and phosphorylation of Smad2, an indicator of TGFβ pathway activation, show a strong correlation and that both positively associate with chemoresistance in colorectal cancer. These findings indicate that the TGFβ/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of PDK4 may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, which warrants the development of PDK4-specific inhibitors.

scholarly journals Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Manuel Valenzuela ◽  
Lorena Bastias ◽  
Iván Montenegro ◽  
Enrique Werner ◽  
Alejandro Madrid ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Grape Juice ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Gene Expressions ◽  
Anticancer Properties

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type.Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells.

Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells

2009 ◽  
Vol 9 (11) ◽  
pp. 1265-1271 ◽  
Author(s):  
Rossella Paolillo ◽  
Caterina Romano Carratelli ◽  
Sabato Sorrentino ◽  
Nello Mazzola ◽  
Antonietta Rizzo
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Lactobacillus Plantarum ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Immunomodulatory Effects ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5608 ◽  
Author(s):  
Hikaru Nagano ◽  
Chisato Tomida ◽  
Naoko Yamagishi ◽  
Shigetada Teshima-Kondo
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Egf Receptor ◽  
Vascular Endothelial Cells ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Colon Cancer Cells ◽  
Proliferation Activity

The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports tumor cell growth in an angiogenesis-dependent manner. In this study, we found angiogenesis-independent novel crosstalk between the VEGF and the EGF pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor (PlGF) activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF/EGF receptor (EGF-R)-dependent manner. Mechanistically, VEGFR-1 interacted with and stabilized EGF-R, leading to increased EGF-R protein levels and prolonged its expression on cell surface plasma membrane. In contrast, VEGFR-1 blockade by a neutralizing antibody and an antagonistic peptide of VEGFR-1 suppressed the complex formation of VEGFR-1 and EGF-R and decreased EGF-R expression via a lysosome-dependent pathway, resulting in the suppression of proliferation activity. Our results indicated that VEGFR-1 regulated EGF-R expression to promote proliferation activity in a cell-autonomous-dependent manner.

Effect of AbGn-7, a glycotope-specific monoclonal antibody, on apoptosis in colon cancer cells and tumor growth in xenograft models

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15118-e15118
Author(s):  
S. Lin ◽  
E. Chiang ◽  
Y. Tsai ◽  
S. Lee ◽  
B. Kuo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Colon Cancer ◽  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Parp Cleavage ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Dose Dependent

e15118 Background: While clinical benefit against colorectal cancer has been observed with therapeutic monoclonal antibodies such as bevacizumab, cetuximab and panituzumab, the death rate of advanced colorectal cancer remains high that warrants further development of more potent therapeutics. Methods: A cell-based immunization approach was used to generate monoclonal antibodies against targets expressed on human colorectal cancer cells. A chimeric monoclonal antibody, AbGn-7, was selected and evaluated for the potential clinical use to treat colorectal cancer. Results: Expression of AbGn-7 antigen: Carbohydrate competition assay demonstrated that AbGn-7 recognizes a Lewis-A-like carbohydrate antigen (AbGn-7 antigen). Immunohistochemical studies showed that AbGn-7 antigen is expressed in colorectal cancer tissue. No significant binding could be detected in non-tumor tissues except in the epithelia of GI track. Effector function of AbGn-7: AbGn-7 triggered dose-dependent apoptosis in COLO 205 colon cancer cell. In addition, AbGn-7 elicited potent complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in a dose-dependent manner. Molecular mechanism of apoptosis induced by AbGn-7: Tunel assay, PARP cleavage assay as well as caspase inhibitor studies demonstrated that AbGn-7 induced apoptosis in COLO 205 colon cancer cells via a caspase-independent pathway. Xenograft study: AbGn-7 alone, or in combination with 5FU-Leucovorin, effectively inhibited the growth of COLO 205 xenograft in SCID mice and prolonged their survival. Conclusions: The results of the present study suggest that AbGn-7 is a potential candidate for effective treatment of colorectal cancer. [Table: see text]

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