scholarly journals Ursolic Acid Induces Apoptosis in Colorectal Cancer Cells Partially via Upregulation of MicroRNA-4500 and Inhibition of JAK2/STAT3 Phosphorylation

2018 ◽  
Vol 20 (1) ◽  
pp. 114 ◽  
Author(s):  
Karam Kim ◽  
Eun Shin ◽  
Ji Jung ◽  
Ji Park ◽  
Dong Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Nuclear Translocation ◽  
Janus Kinase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Parp Cleavage ◽  
Stat3 Phosphorylation ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Though ursolic acid (UA) isolated from Oldenlandia diffusa was known to exhibit anti-cancer, anti-inflammatory, and anti-obesity effects, the underlying antitumor mechanism of ursolic acid was not fully understood to date. Thus, in the present study, the apoptotic mechanism of ursolic acid was elucidated in HCT116 and HT29 colorectal cancer cells in association with STAT3 and microRNA-4500 (miR-4500) by MTT assay, Terminal deoxynucleotidyl transferase-dT-mediated dUTP nick end labelling (TUNEL) assay, cell cycle analysis, immunofluorescence, and Western blotting. Ursolic acid significantly exerted cytotoxicity, increased TUNEL positive cells and sub-G1 apoptotic portion, induced cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) and caspase 3 in HCT116 and HT29 cells. Of note, ursolic acid attenuated the expression of anti-apoptotic proteins such as Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) and also blocked nuclear translocation of STAT3 in colorectal cancer cells. Notably, ursolic acid increased the expression level of miR-4500 in HCT116 cells by qRT-PCR analysis and conversely miR-4500 inhibitor reversed cytotoxic, anti-proliferative, and apoptotic effects by increasing TUNEL positive cells, PARP cleavage and inhibiting p-STAT3 in ursolic acid treated colorectal cancer cells. Overall, our findings provide evidence that usolic acid induces apoptosis in colorectal cancer cells partially via upregulation of miR-4500 and inhibition of STAT3 phosphorylation as a potent anti-cancer agent for colorectal cancer therapy.

scholarly journals Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells

2006 ◽  
Vol 60 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Chong-Zhi Wang ◽  
Xiaoji Luo ◽  
Bin Zhang ◽  
Wen-Xin Song ◽  
Ming Ni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells

scholarly journals Acetylshikonin Induces Apoptosis in Human Colorectal Cancer HCT-15 and LoVo Cells via Nuclear Translocation of FOXO3 and ROS Level Elevation

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Heui Min Lim ◽  
Jongsung Lee ◽  
Myeong Jin Nam ◽  
See-Hyoung Park
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Human Colorectal Cancer ◽  
Antiproliferative Effects ◽  
Lovo Cells ◽  
Colorectal Cancer Cells

Acetylshikonin, a naphthoquinone, is a pigment compound derived from Arnebia sp., which is known for its anti-inflammatory potential. However, its anticarcinogenic effect has not been well investigated. Thus, in this study, we focused on investigating its apoptotic effects against HCT-15 and LoVo cells, which are human colorectal cancer cells. MTT assay, cell counting assay, and colony formation assay have shown acetylshikonin treatment induced cytotoxic and antiproliferative effects against colorectal cancer cells in a dose- and time-dependent manner. DNA fragmentation was observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Also, the increase of subG1 phase in cell cycle arrest assay and early/late apoptotic rates in annexin V/propidium iodide (PI) double staining assay was observed, which indicates an apoptotic potential of acetylshikonin against colorectal cancer cells. 2 ′ ,7 ′ -Dichlorofluorescin diacetate (DCF-DA) staining was used to evaluate reactive oxygen species (ROS) generation in acetylshikonin-treated colorectal cancer cells. Fluorescence-activated cell sorting (FACS) analysis showed that acetylshikonin induced an increase in reactive oxygen species (ROS) levels and apoptotic rate in a dose- and time-dependent manner in HCT-15 and LoVo cells. In contrast, cotreatment with N-acetyl cysteine (NAC) has reduced ROS generation and antiproliferative effects in colorectal cancer cells. Western blotting analysis showed that acetylshikonin treatment induced increase of cleaved PARP, γH2AX, FOXO3, Bax, Bim, Bad, p21, p27, and active forms of caspase-3, caspase-7, caspase-9, caspase-6, and caspase-8 protein levels, while those of inactive forms were decreased. Also, the expressions of pAkt, Bcl-2, Bcl-xL, peroxiredoxin, and thioredoxin 1 were decreased. Furthermore, western blotting analysis of cytoplasmic and nuclear fractionated proteins showed that acetylshikonin treatment induced the nuclear translocation of FOXO3, which might result from DNA damage by the increased intracellular ROS level. This study represents apoptotic potential of acetylshikonin against colorectal cancer cells via translocation of FOXO3 to the nucleus and upregulation of ROS generation.

scholarly journals Comparative proteomics—network analysis of proteins responsible for ursolic acid–induced cytotoxicity in colorectal cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769501 ◽  
Author(s):  
Qiaoyan Cai ◽  
Jing Lin ◽  
Ling Zhang ◽  
Jiumao Lin ◽  
Lili Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Protein Interactions ◽  
Direct Interaction ◽  
Interaction Network ◽  
Two Dimensional Gel Electrophoresis ◽  
Cellular Targets ◽  
Protein Protein Interaction ◽  
Colorectal Cancer Cells

Ursolic acid is a key active compound present in many medicinal herbs that have been widely used in traditional Chinese medicine for the clinical treatment of various cancers. However, the precise mechanisms of its antitumor activity have been poorly understood. To identify the cellular targets of ursolic acid, two-dimensional gel electrophoresis combined with mass spectrometry was performed in this study, which identified 15 proteins with significantly altered levels in protein expression. This demonstrated that ursolic acid–induced cytotoxicity in colorectal cancer cells involves dysregulation in protein folding, signal transduction, cell proliferation, cell cycle, and apoptosis. Corresponding protein regulation was also confirmed by Western blotting. Furthermore, the study of functional association between these 15 proteins revealed that 10 were closely related in a protein–protein interaction network, whereby the proteins either had a direct interaction with each other or were associated via only one intermediary protein. In this instance, the ATP5B/CALR/HSP90B1/HSPB1/HSPD1-signaling network was revealed as the predominant target which was associated with the majority of the observed protein–protein interactions. As a result, the identified targets may be useful in explaining the anticancer mechanisms of ursolic acid and as potential targets for colorectal cancer therapy.

scholarly journals The anti-cancer activity of an andrographolide analogue functions through a GSK-3β-independent Wnt/β-catenin signaling pathway in colorectal cancer cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Somrudee Reabroi ◽  
Rungnapha Saeeng ◽  
Nittaya Boonmuen ◽  
Teerapich Kasemsuk ◽  
Witchuda Saengsawang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Gsk 3Β ◽  
Cancer Activity

scholarly journals Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gracielle C. de Almeida ◽  
Luiz F. S. Oliveira ◽  
Danilo Predes ◽  
Harold H. Fokoue ◽  
Ricardo M. Kuster ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

scholarly journals Parthenolide Induces Oxidative Stress and Impedes Cell Migration by Suppressing Wnt Pathway and Epithelial-Mesenchymal-Transition (EMT) in HCT-116 Metastatic Colorectal Cancer Cells

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2313-2323
Author(s):  
Sananda Dey ◽  
Nensina Murmu ◽  
Mijanur R Molla ◽  
Sandeep K Dash ◽  
Biplab Giri
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Pcr Analysis ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Hct 116

Colorectal cancer (CRC) is a vital cause of cancer morbidity and mortality. 50% of CRC patients suffer from an aggressive metastatic disease which ultimately fallout in death. In metastatic cancer, tumour cells migrate, invade, and finally colonise to the distant organ by degrading their attachments with the extracellular matrix. Parthenolide (PTL) is a secondary metabolite of feverfew (Tanacetum parthenium) plant. It shows its cytotoxic effect towards cancer cells via different cellular signalling pathways like inhibition of NF-κB, STAT3, MAPK, JNK pathways, activation of p53 etc. In the present study, we have assessed anti-cancer and anti-metastatic potential of PTL against human HCT-116 metastatic colorectal cancer cells. Analysis of cellular oxidative status (GSH/GSSG) of PTL treated HCT-116 cells showed a significant decrease (p<0.05) in GSH level while GSSG level was increased significantly (p<0.05) on PTL treatment. PTL also increased the amount of intracellular reactive oxygen species. The qRT-PCR analysis revealed that PTL down-regulates c-fos, c-jun and N-cadherin expression and up-regulates E-cadherin expression indicating inhibition of cell migration and metastasis by EMT pathway. PTL inhibited the MMP-9 expression in a dose-dependent fashion and inhibited cancer cell migration by regulating Wnt/β-catenin signalling through the up-regulation of DKK-1 protein expression indicating PTL has a promising anti-cancer potential against HCT-116 metastatic colorectal carcinoma cells. 

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