The potential therapeutic actions of melatonin in colorectal cancer

Author(s):  
Kian Chung Chok ◽  
Chew Hee Ng ◽  
Rhun Yian Koh ◽  
Khuen Yen Ng ◽  
Soi Moi Chye

Abstract Colorectal cancer (CRC) is the third most common cancer and lethal disease worldwide. Melatonin, an indoleamine produced in pineal gland, shows anticancer effects on a variety of cancers, especially CRC. After clarifying the pathophysiology of CRC, the association of circadian rhythm with CRC, and the relationship between shift work and the incidence of CRC is reviewed. Next, we review the role of melatonin receptors in CRC and the relationship between inflammation and CRC. Also included is a discussion of the mechanism of gene regulation, control of cell proliferation, apoptosis, autophagy, antiangiogenesis and immunomodulation in CRC by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as comprehensive reference for the various mechanisms of action of melatonin against CRC, and as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for CRC.

2012 ◽  
Vol 6 ◽  
pp. CMO.S7432 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Albert Craig Lockhart

Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chao-Tao Tang ◽  
Jing Yang ◽  
Zi-De Liu ◽  
Youxiang Chen ◽  
Chunyan Zeng

AbstractColorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression of RNF31 in CRC tissue samples via immunohistochemistry and elucidated the function of RNF31 in CRC cells by constructing a cell model with RNF31 depletion. A cycloheximide (CHX)-chase analysis and immunofluorescence assays were conducted to demonstrate that TA can promote RNF31 degradation by activating autophagy. We used the PharmMapper website to predict targets of TA and identified RNF31. CHX-chase experiments showed that TA could facilitate RNF31 degradation, which was inhibited by the administration of chloroquine. Immunofluorescence assays showed that RNF31 protein was colocalized with LC3I/II and p62, suggesting that TA promoted RNF31 degradation by activating autophagy. We also found that CRC patients with RNF31 overexpression had poorer survival than those with low RNF31 expression. The results of the CHX-chase experiment showed that depletion of RNF31 alleviated p53 degradation, which was inhibited by MG132. A series of co-immunoprecipitation (Co-IP) assays revealed that RNF31 interacts with p53 and promotes p53 ubiquitination and degradation. A Co-IP assay performed with a truncated RNF31 plasmid showed that the PUB domain interacts with p53. Moreover, the PUB domain is the key structure in the induction of p53 ubiquitination. Our findings reveal a key role of RNF31 in CRC cell growth and indicate a mechanism through which TA inhibits cell growth.


2020 ◽  
Author(s):  
Yuanyi Yue ◽  
Qiang Zhang ◽  
Li Xiao

Abstract Objectives: Colorectal cancer (CRC) is recognized as the third most common cancer worldwide. Recently, emerging evidence showed that microRNA (miRNA) A-to-I editing plays crucial roles in cancer prognosis as well as cancer therapy. However, the relationship between CRC and miRNA editing remains not fully understood. Herein, we presented the first comprehensive analysis of miRNA editing events in CRC. Methods: Using patient data from The Cancer Genome Atlas (TCGA), we performed editing events and detected the expression levels of miR-589-5p. Results: we identified both editing events and the expression levels of miR-589-5p are significantly associated with Consensus Molecular Subtyping (CMS), especially for CMS4. The editing and expression levels of miR-589-5p impact almost completely different sets of gene expression, indicating the edited miR-589-5p plays a different role in CRC progression, compared to the wildtype miR-589-5p. Conclusions: In conclusion, our study provided the first association of miRNA editing and CRC. We demonstrated that expression and editing level of miR‑589‑5p may work as a novel biomarker for both prognosis and diagnosis in CRC.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Aga Syed Sameer ◽  
Saniya Nissar

Toll-like receptors (TLRs) are the important mediators of inflammatory pathways in the gut which play a major role in mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of colorectal cancer (CRC). CRC is one of the major malignancies affecting the worldwide population and is currently ranking the third most common cancer in the world. In this review, we have attempted to discuss the structure, functions, and signaling of TLRs in comprehensive detail together with the role played by various TLR gene SNPs in CRC susceptibility.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.


2021 ◽  
Vol 10 (1) ◽  
pp. 15-40
Author(s):  
Archana Prasad

This article explores some questions arising from recent debates on patriarchy and capitalism. The focus is on the role of women in communist-led peasant movements in India and the implications of such struggles on the project of women’s emancipation. The first section lays out a framework for discussing the interface between class consciousness and the anti-patriarchal project, whereby patriarchy is located within the structural contradictions arising out of the contestations within the process of accumulation. The second section documents the historical context, focusing on the relationship between land reforms and social transformation in semi-feudal and early capitalist contexts, and analyzes the extent to which communist-led struggles are anti-patriarchal in character. The third section turns to the participation of women in the contemporary struggles of both agricultural workers and peasant movements and underlines the new emerging dialectics between women’s and peasant organizations under a neoliberal state and with deepening agrarian distress.


2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-βcan be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.


2020 ◽  
Vol 56 (1) ◽  
pp. 15
Author(s):  
Husin Thamrin ◽  
Khafidhotul Ilmiah ◽  
Ni Wajan Tirthaningsih

Colorectal cancer has became burden in the world.The latest study shows that colorectal cancer is the third most common cancer in men and second most common cancer in women globally. There are difference characteristic of epidemiology in every countries. Moreover, there is no study that represents epidemiology of colorectal cancer in Indonesia yet, especially in East Java. The aim of this study was to describe colorectal tumor profile by age and gender in Gastroentero-Hepatology Center, Dr Soetomo Hospital. This study has received a certificate of Ethical Clearance No.273/Panke.KKE/IV/2015, a descriptive retrospective study. We collected data using medical records, and patients who have been colonoscopy examination and suspected colorectal tumor were included. There were 201 patients, divided to 100 males and 101 females. The peak of incidence was on 51-60 years old group, but on the 31-40 years old incidence of colorectal tumor was increased. The youngest patient was 17 years old. And tumors are more likely develop in distal area, especially in rectum. This study shows a different characteristic profile of colorectal tumor, where tumor is developed at young people and there is no significant difference between male and female for the incidence.


2020 ◽  
Vol 18 (1) ◽  
pp. 25-27
Author(s):  
Anna Marija Lescinska ◽  
Valerija Grakova ◽  
Aleksandrs Malasonoks ◽  
Armands Sivins

SummaryThe case report demonstrates painstaking, one step at a time multitherapy for the third most common cancer and the third cause of cancer death in western countries – colorectal cancer. Multitherapeutic approach at specialized centers for the treatment of colorectal cancer is the cornerstone for reaching favorable treatment results and prognosis.


2020 ◽  
Vol 21 (15) ◽  
pp. 5353 ◽  
Author(s):  
Hsiuying Wang

Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is rising in developing countries. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, de-regulated apoptotic signaling allows cancer cells to escape this signaling, leading to therapeutic resistance. Treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.


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