Quercetin-Mediated Apoptosis and Cellular Senescence in Human Colon Cancer

2020 ◽  
Vol 20 (11) ◽  
pp. 1387-1396 ◽  
Author(s):  
Serpil Özsoy ◽  
Eda Becer ◽  
Hilal Kabadayı ◽  
Hafize S. Vatansever ◽  
Sevinç Yücecan
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cellular Senescence ◽  
Colon Adenocarcinoma ◽  
Cyclin B1 ◽  
Tunel Staining ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Lamin B1

Background: Quercetin is a flavonol from the flavonoid group of polyphenols, which positively affects human health due to its anti-cancer, anti-inflammatory, anti-microbial and cardioprotective effects. The effects of phenolic compounds, including quercetin, on programmed cell death and cellular senescence, have been the subject of research in recent years. Objective: In this study, we aimed to investigate the effects of quercetin on cell viability, apoptosis and cellular senescence in primary (Colo-320) and metastatic (Colo-741) colon adenocarcinoma cell lines. Methods: Cytotoxicity was analyzed via MTT assay in Colo-320 and Colo-741 cell lines. After quercetin treatment, cell ularsenescence and apoptosis were evaluated by TUNEL staining, X-Gal staining and indirect peroxidase technique for immunocytochemical analysis of related proteins such as Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1. Results: The effective dose for inhibition of cell growth in both cell lines was determined to be 25μg/ml quercetin for 48 hours. Increased Baximmunoreactivityfollowingquercetin treatment was significant in both Colo-320 and Colo-741 cell lines, but decreased Bcl-2 immunoreactivitywas significant only in theColo-320 primary cell line. In addition, after quercetin administration, the number of TUNEL positive cells and, immunoreactivities for p16, Lamin B1 and cyclin B1 in both Colo-320 and Colo-741 cells increased. Conclusion: Our results suggest that quercetin may only induce apoptosis in primary colon cancer cells. Furthermore, quercetin also triggered senescence in colon cancer cells, but some cells remained alive, suggesting that colon cancer cells might have escaped from senescence.

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.

Incomplete processing of progastrin expressed by human colon cancer cells: role of noncarboxyamidated gastrins

1994 ◽  
Vol 266 (3) ◽  
pp. G459-G468 ◽  
Author(s):  
P. Singh ◽  
Z. Xu ◽  
B. Dai ◽  
S. Rajaraman ◽  
N. Rubin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Colon ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

Gastrin is mitogenic for several colon cancers. To assess a possible autocrine role of gastrin in colon cancers, we examined human colon cancer cell lines for expression of gastrin mRNA and various forms of gastrin. Gastrin mRNA was not detected in the majority of colon cancer cell lines by Northern hybridization but was detected in all human colon cancer lines by the sensitive method of reverse transcriptase-polymerase chain reaction (PCR). Gastrin mRNA was quantitated by the competitive PCR method. The majority of cell lines expressed very low levels of gastrin mRNA (< 1-5 copies/cell); only one cell line expressed > 20 copies/cell. The mature carboxyamidated form of gastrin was not detected in any of the cell lines by radioimmunoassay or immunocytochemistry. Results suggested that either gastrin mRNA expressed by colon cancer cells was altered (mutated) or posttranslational processing of progastrin was incomplete. Gastrin cDNA from all the colon cancer cell lines had an identical sequence to the published sequence of human gastrin cDNA. Specific antibodies against precursor forms of gastrin were used, and significant concentrations of nonamidated (glycine-extended) and prepro forms of gastrin were measured in tumor extracts of representative colon cancer cell lines. The presence of precursor forms of gastrin suggested a lack of one or more of the processing enzymes and/or cofactors. Significant concentrations of the processing enzyme (peptidylglycine alpha-amidating monooxygenase) were detected in colon cancer cells by immunocytochemistry. Therefore, lack of other cofactors or enzymes may be contributing to incomplete processing of precursor forms of gastrin, which merits further investigation. Since low levels of gastrin mRNA were expressed by the majority of human colon cancer cell lines and progastrin was incompletely processed, it seems unlikely that gastrin can function as a viable autocrine growth factor for colon cancer cells. High concentrations of glycine-extended gastrin-17 (GG) (> 10(-6) M) were mitogenic for a gastrin-responsive human colon cancer (DLD-1) cell line in vitro. It remains to be seen if GG or other precursor forms of gastrin are similarly mitogenic in vivo, which may then lend credibility to a possible autocrine role of gastrinlike peptides in colon cancers.

scholarly journals Activation of PERK Contributes to Apoptosis and G2/M Arrest by Microtubule Disruptors in Human Colorectal Carcinoma Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 97 ◽  
Author(s):  
Ming-Shun Wu ◽  
Chih-Chiang Chien ◽  
Ganbolor Jargalsaikhan ◽  
Noor Andryan Ilsan ◽  
Yen-Chou Chen
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
B Cell Lymphoma ◽  
Human Colon ◽  
Cyclin B1 ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Jnk Inhibitors ◽  
Induced Apoptosis ◽  
Human Colon Cancer Cells

Microtubule-targeting agents (MTAs) are widely used in cancer chemotherapy, but the therapeutic responses significantly vary among different tumor types. Protein kinase RNA-like endoplasmic reticular (ER) kinase (PERK) is an ER stress kinase, and the role of PERK in the anticancer effects of MTAs is still undefined. In the present study, taxol (TAX) and nocodazole (NOC) significantly induced apoptosis with increased expression of phosphorylated PERK (pPERK; Tyr980) in four human colon cancer cell lines, including HCT-15, COLO205, HT-20, and LOVO cells. Induction of G2/M arrest by TAX and NOC with increases in phosphorylated Cdc25C and cyclin B1 protein were observed in human colon cancer cells. Application of the c-Jun N-terminal kinase (JNK) inhibitors SP600125 (SP) and JNK inhibitor V (JNKI) significantly reduced TAX- and NOC-induced apoptosis and G2/M arrest of human colon cancer cells. Interestingly, TAX- and NOC-induced pPERK (Tyr980) protein expression was inhibited by adding the JNK inhibitors, SP and JNKI, and application of the PERK inhibitor GSK2606414 (GSK) significantly reduced apoptosis and G2/M arrest by TAX and NOC, with decreased pPERK (Tyr980) and pJNK, phosphorylated Cdc25C, and Cyc B1 protein expressions in human colon cancer cells. Decreased viability by TAX and NOC was inhibited by knockdown of PERK using PERK siRNA in COLO205 and HCT-15 cells. Disruption of the mitochondrial membrane potential and an increase in B-cell lymphoma-2 (Bcl-2) protein phosphorylation (pBcl-2; Ser70) by TAX and NOC were prevented by adding the PERK inhibitor GSK and JNK inhibitor SP and JNKI. A cross-activation of JNK and PERK by TAX and NOC leading to anti-CRC actions including apoptosis and G2/M arrest was first demonstrated herein.

scholarly journals Trolox induces inhibition of cell proliferation and apoptosis in human colon cancer cells

2015 ◽  
Vol 10 (4) ◽  
pp. 931 ◽  
Author(s):  
Li-Guang Yang ◽  
Xiang-An Tian ◽  
Xiao-Yan Li ◽  
Jian-Guo Huang ◽  
Nai-Qing Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

<p class="Abstract">In the present study, the effect of trolox on human colon cancer cell lines was investigated. The results revealed that trolox treatment caused inhibition of cell growth in T84 and HCT-15 colon cancer cell lines in a dose-dependent manner. The inhibition was significant at 50 µM of trolox after 48 hours in both cell lines. Trolox treatment promoted expression of p38 and inhibited expression of survivin and Akt. It also induced cleavage of PARP and caspase-3 and ultimately induced apoptosis in T84 and HCT-15 cells. The tumor growth was inhibited significantly in the xenotransplanted mice on treatment with trolox compared to the control group. Since trolox treatment exhibits inhibitory effect on the proliferation of colon cancer cells and inhibits tumor growth in vivo therefore, can be of therapeutic importance for the treatment of colon cancer.</p><p> </p>

CCDC12 Promotes Tumor Development and Invasion Through the Snail Pathway in Colon Adenocarcinoma

2020 ◽  
Author(s):  
Fengying Du ◽  
Leping Li ◽  
Qiang Wang ◽  
Wenting Pei ◽  
Hongqing Zhuo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Lovo Cell ◽  
Eqtl Analysis ◽  
Colon Cancer Cells ◽  
Knock Down ◽  
Sw480 Cells ◽  
Mesenchymal Transformation

Abstract Background: To determine the role of Coiled-coil domain containing 12 (CCDC12) in colon adenocarcinoma (COAD).Methods: We used integrative expression Quantitative Trait Loci (eQTL) analysis to identify risk single nucleotide polymorphisms (SNPs) and associated genes. Immunohistochemical staining (IHC) and western blotting (WB) were used to detect CCDC12 expression. We selected SW480 and LOVO cell lines to knock down CCDC12, while HCT116 and SW480-KD cell lines were up-regulated. Then performed functional studies and established a xenograft tumor model in BALB/c mice. Four plex Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) assays were performed to determine its function and potential regulatory mechanism. Overexpressed Snail and knocked down CCDC12 subsequently in SW480 cells to find them association.Results: Integrative eQTL analysis found that rs8180040 was significantly associated with CCDC12 in COAD patients. IHC and WB confirmed CCDC12 was highly expressed in COAD tissues (IHC 51/75 vs 8/75, WB 10/12 vs 2/12). This was consistent with RNA-Seq data from TCGA database (P value < 0.001). Knockdown of CCDC12 could significantly reduce proliferation, migration, invasion and tumorigenicity of colon cancer cells, while exogenous overexpression of CCDC12 had the opposite effect. iTRAQ assays demonstrated that overexpression of CCDC12 would change proteins on adherens junction pathway. Overexpression of Snail did not significantly change CCDC12 levels in SW480 cells, while knock down of CCDC12 reduced that of Snail.Conclusions: CCDC12 plays a significant role in tumorigenesis, development and invasion of COAD and may affect the epithelial to mesenchymal transformation process of colon cancer cells by regulating the Snail pathway.

scholarly journals Cordyceps militarisGrown on Germinated Soybean Induces G2/M Cell Cycle Arrest through Downregulation of Cyclin B1 and Cdc25c in Human Colon Cancer HT-29 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammad Lalmoddin Mollah ◽  
Dong Ki Park ◽  
Hye-Jin Park
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Cyclin B1 ◽  
Treated Group ◽  
Colon Cancer Cells ◽  
M Cell ◽  
Human Colon Cancer ◽  
Germinated Soybean ◽  
Ht 29

Cordyceps militaris(CM) is an insect-borne fungus that has been used in traditional Chinese medicine because of its wide range of pharmacological activities. In this paper, we studied CM grown on germinated soybean (GSC) and investigated the possible mechanisms underlying antiproliferative effect of GSC on HT-29 human colon cancer cells. In comparison with CM extracts and germinated soybean (GS) BuOH extracts, BuOH extracts of GSC showed remarkable inhibitory and antiproliferative effects on HT-29 colon cancer cells. After GSC treatment, HT-29 cells became smaller and irregular in shape. High G2/M phase cell populations were observed in the GSC-treated group. The levels of cyclin B1 and Cdc25 in the GSC-treated group were lower than those in the control group. These findings suggest that GSC BuOH extracts might act as an effective anti-proliferative agent by inducing G2/M cell cycle arrest in colon cancer cells.

scholarly journals α-Hederin Arrests Cell Cycle at G2/M Checkpoint and Promotes Mitochondrial Apoptosis by Blocking Nuclear Factor-κB Signaling in Colon Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dongdong Sun ◽  
Weixing Shen ◽  
Feng Zhang ◽  
Huisen Fan ◽  
Jiani Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Cyclin B1 ◽  
New Drugs ◽  
Nuclear Factor ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sw620 Cells

Colon cancer represents the third most common malignancy worldwide. New drugs with high efficaciousness and safety for the treatment of colon cancer are urgently needed in clinical context. Here, we were aimed to evaluate the antitumor activity of the natural compound α-hederin in human colon cancer cells. We treated SW620 cells with interleukin-6 (IL-6) in vitro to mimic the paracrine inflammatory microenvironment of tumor cells. α-Hederin concentration dependently reduced the viability of IL-6-stimulated SW620 cells. α-Hederin increased the number of IL-6-stimulated SW620 cells at the G2/M phase and reduced the mRNA and protein expression of cyclin B1 and CDK1. Moreover, α-hederin induced apoptosis and loss of mitochondrial membrane potential in IL-6-stimulated SW620 cells. α-Hederin downregulated Bcl-2 expression, upregulated Bax expression, and promoted cytochrome c release from mitochondria into cytoplasm. Additionally, α-hederin elevated the levels of cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP, but had little effects on the levels of cleaved-caspase-8. Moreover, α-hederin prevented the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of IκBα and IKKα, suggesting the blockade of NF-κB signaling. NF-κB inhibitor PDTC not only produced similar proapoptotic effects on IL-6-stimulated SW620 cells as α-hederin did, but also synergistically enhanced α-hederin’s proapoptotic effects. Furthermore, α-hederin inhibited the phosphorylation of ERK in IL-6-stimulated SW620 cells, which was involved in α-hederin blockade of NF-κB nuclear translocation. Altogether, α-hederin suppressed viability, induced G2/M cell cycle arrest, and stimulated mitochondrial and caspase-dependent apoptosis in colon cancer cells, which were associated with disruption of NF-κB and ERK pathways, suggesting α-hederin as a promising candidate for intervention of colon cancer.

scholarly journals The Effect of SLC2A3 Expression on Cisplatin Resistance of Colorectal Cancer Cells

2021 ◽  
Author(s):  
Yan Li ◽  
Hailong Lei ◽  
Ming Zhang ◽  
Guangming Wu ◽  
Caiyun Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Western Blotting ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Colorectal Cancer Cells ◽  
Human Colon Cancer Cells

Background: To study the molecular mechanism of cisplatin chemotherapy resistance in colorectal cancer cells and to explore the effect of miRNA in regulating the expression of glucose transporter 3 (SLC2A3) and the proliferation and migration of colon cancer cells. Methods: All samples were obtained from the People’s Hospital of Wuhai, Wuhai, China between June 2019 and June 2020. Real-time quantitative PCR (qRT-PCR) was carried out to check the expression of miR-103a in these cell lines. Western blotting and Luciferase reporter gene detection confirmed the regulation of the miR-103a/SLC2A3 axis. Western blotting detected the activation of SLC2A3, caspased-9 and -3. Results: The expression of SLC2A3 protein in colon cancer cell lines was significantly higher than that of normal colon cancer cells, while the expression of SLC2A3 miRNA showed no significant difference (P<0.05). Then, through clone formation analysis, SLC2A3 was closely related to the proliferation of human colon cancer cells. Functional recovery experiments showed that increasing the expression of miR-103a could reverse the abnormal proliferation caused by overexpression of SLC2A3. Conclusion: Overall, miR-103a can inhibit the proliferation of human colon cancer cells by targeting SLC2A3, and this result will provide a potential target for the treatment of colon cancer.

Gland formation of human colon cancer cells combined with foetal rat mesenchyme in organ culture: an ultrastructural study

1987 ◽  
Vol 87 (5) ◽  
pp. 615-621
Author(s):  
H. Fukamachi ◽  
T. Mizuno ◽  
Y.S. Kim
Keyword(s):  
Colon Cancer ◽  
Organ Culture ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Foetal Rat ◽  
Glandular Structures ◽  
Human Colon Cancer Cells

The morphogenetic potential of human colon cancer cells was examined by combining cells with foetal rat mesenchyme in organ culture. Out of four cell lines examined, LS174T cells formed glandular structures composed of a simple columnar or cuboidal epithelium with a lumen in the centre of the cell mass. Ultrastructurally, these gland-forming LS174T cells exhibited polarity, with nuclei located basally, microvilli projecting into the lumen, tight junctions at the cell—cell junction facing the lumen, desmosomes at the subluminal region, and basal laminae at the epithelial-mesenchymal interface. Other cell lines did not form such glandular structures, while some cells could form microvilli, tight junctions or basal laminae, which were arranged randomly. It is concluded that it is not the existence but the ordered arrangement of these structures that is essential for gland formation by epithelial cells. The mechanism of gland formation is discussed with special reference to the arrangement of different structures.

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