scholarly journals Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 376
Author(s):  
Muhammad Azizan Samad ◽  
Mohd Zuwairi Saiman ◽  
Nazia Abdul Majid ◽  
Saiful Anuar Karsani ◽  
Jamilah Syafawati Yaacob

Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 ± 0.89 µg/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 ± 3.12 µg/mL) and silymarin (>200 µg/mL). Further analyses exhibited that berberine treatment caused G0/G1 phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Dany Muhammad Daffa ◽  
Muhammad Hasan Bashari ◽  
Eko Fuji Ariyanto ◽  
Tenny Putri ◽  
Nurul Qomarilla

Background: Colorectal cancer is the second leading cause of mortality and the most prevalent cancer worldwide. Most patients, who come with late-stage, have ineffective treatments and some side effects in chemotherapy. Aaptos suberitoides has potential anti-cancer effects due to its bioactive compounds such as aptamine. This study aimed to evaluate the migration inhibition effect of Aaptos suberitoides fraction in HCT-116 cell line.Methods: This study was an experimental study. Aaptos suberitoides specimen was taken in Tinjil Island and fractionated with ethyl acetate. HCT-116 cell line was added with Aaptos suberitoides fraction and cellular migration activity was observed in 48 hours of which the scratch assay was performed. The gap closure area was determined with ImageJ software.Results: The data showed that a low concentration of Aaptos suberitoides fraction inhibited migration activity in HCT-116 cell line as follow; 1 and 5 mg/L Aaptos suberitoides fraction inhibit 3-4 % cancer cell migration in 24 hours, and 10-11% inhibition in 48 hours, respectively. However, 10 mg/L fraction concentration only inhibited 7-14% of the migration effect.Conclusion: Aaptos suberitoides fraction suggests insignificant migration inhibition in colorectal cancer cells and only inhibits less than 15 % HCT-116 cell line.


2002 ◽  
Vol 184 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Cheppail Ramachandran ◽  
Hugo B Fonseca ◽  
Perseus Jhabvala ◽  
Enrique A Escalon ◽  
Steven J Melnick

2021 ◽  
Author(s):  
Veeranna Yempally ◽  
Queenie Fernandez ◽  
Lobna Safwan Al_Zaidan ◽  
Varghese Inchakalody ◽  
Maysaloun Merhi ◽  
...  

Author(s):  
Fahad M. Almutairi ◽  
Ayat G. Ali ◽  
Abdou O. Abdelhamid ◽  
Adel I. Alalawy ◽  
Mai K. Bishr ◽  
...  

Background: Defects in the physiological mechanisms of apoptosis are one of the pivotal factors implicated in carcinogenesis. Thus, the development of novel compounds that target various apoptotic pathways has provided promising anticancer therapeutic opportunities. Objective: This study explores the cytotoxic effects of a novel unsymmetrical azine against specific cancer cell lines and investigates the mechanism of cytotoxicity. Methods: Molecular modeling was used to test the binding affinity of four new unsymmetrical azines to a model of an apoptosis inhibitor protein (XIAP). The compound with the highest binding affinity, C4, was further tested on different cell lines. Real-time polymerase chain reaction (PCR) and transmission electron microscope (TEM) were used to study apoptosis induction biochemically and morphologically. Results: In comparison to cisplatin as a control, the compound C4 exhibited notable cytotoxicity against all tested cancer cell lines, especially the human colorectal carcinoma cell line (HCT-116). Furthermore, C4-treated cells demonstrated marked overexpression of the pro-apoptotic proteins Bax and caspase-3 as well as the tumor suppressor p53. On the other hand, the expression of the anti-apoptotic protein Bcl-2 was inhibited. On TEM examination, C4-treated HCT-116 cells showed classical structural signs of apoptosis. Conclusion: This study identifies a novel azine (C4) which induces remarkable cytotoxicity against colorectal carcinoma cell line, mediated through apoptosis induction. These novel insights suggest C4 as a promising therapeutic agent in colorectal cancer.


2015 ◽  
Vol 26 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Ladan Teimoori-Toolabi ◽  
Saba Hashemi ◽  
Kayhan Azadmanesh ◽  
Farnaz Eghbalpour ◽  
Farnaz Safavifar ◽  
...  

Author(s):  
İlknur Çınar Ayan ◽  
Sümeyra Çetinkaya ◽  
Hatice Gül Dursun ◽  
Canan Eroğlu Güneş ◽  
Seda Şirin

Background: In the treatment of colorectal cancer (CRC), the search for new antineoplastic drugs with fewer side effects and more effectiveness continues. A significant part of these pursuits and efforts focus on medicinal herbs and plant components derived from these plants. A. ketenoglui is one of these medicinal plants, and its anticancer potential has never been studied before. Methods: The phenolic and flavonoid content, and antioxidant activity of A. ketenoglui extracts were determined. The phytochemical profiling and quantification analysis of major components were performed by HPLC-ESI-Q-TOF-MS. Cytotoxicity, proliferation, apoptosis and cell cycle were evaluated to reveal the anticancer activity of the extract on CRC cells (HCT 116 and HT-29). The determined anticancer activity was confirmed by mRNA (RT-qPCR) and protein (Western blotting) analyzes. Results: A. ketenoglui methanol extract was found to have high phenolic (281.89±0.23) and flavonoid (33.80±0.15) content and antioxidant activity (IC50 40.03±0.38). According to the XTT assay, the extract has strong cytotoxic activity (IC50 350 µM in HCT 116 and IC50 263 µM in HT-29 cell line). The compounds most commonly found in the plant are, in descending order, chlorogenic acid, apigenin, genistin, baicalin, eupatorin, casticin, and luteolin. In flowcytometric analysis, the extract was found to induce greater apoptosis and cell cycle arrest in both cell lines than in both control and positive control (casticin). According to the results of the mRNA expression analysis, the extract treatment upregulated the expression of the critical genes of the cell cycle and apoptosis, such as p53, p21, caspase-3, and caspase-9. In protein expression analysis, an increase in caspase-3 and p53 expression was observed in both cell lines treated with the extract. In addition, caspase-9 expression was increased in HT-29 cells. Conclusion: The findings show that A. ketenoglui has an anticancer potential by inducing apoptosis and arresting the cancer cell cycle and may be promising for CRC therapy. This potential of the plant is realized through the synergistic effects of its newly identified components.


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