scholarly journals Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review

2020 ◽  
Vol 9 (1) ◽  
pp. 2-18 ◽  
Author(s):  
Karthikkumar Venkatachalam ◽  
Ramachandran Vinayagam ◽  
Mariadoss Arokia Vijaya Anand ◽  
Nurulfiza Mat Isa ◽  
Rajasekar Ponnaiyan

Abstract 1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

2021 ◽  
Vol 14 ◽  
Author(s):  
Lydia Amari ◽  
Marc Germain

Extracellular vesicles (EVs) have emerged in the last decade as critical cell-to-cell communication devices used to carry nucleic acids and proteins between cells. EV cargo includes plasma membrane and endosomal proteins, but EVs also contain material from other cellular compartments, including mitochondria. Within cells, mitochondria are responsible for a large range of metabolic reactions, but they can also produce damaging levels of reactive oxygen species and induce inflammation when damaged. Consistent with this, recent evidence suggests that EV-mediated transfer of mitochondrial content alters metabolic and inflammatory responses of recipient cells. As EV mitochondrial content is also altered in some pathologies, this could have important implications for their diagnosis and treatment. In this review, we will discuss the nature and roles of mitochondrial EVs, with a special emphasis on the nervous system.


Author(s):  
Kanya Thongra-ar ◽  
Piyanuch Rojsanga ◽  
Savita Chewchinda ◽  
Supachoke Mangmool ◽  
Pongtip Sithisarn

The objects of this study were to determine the effects to reactive oxygen species and antioxidant enzymes levels in HEK-293 cells and inhibition of α-glucosidases and α-amylase enzymes of extracts from Persicaria odorata or phak phaeo. The ethanol extracts from the leaves and the stems of phak phaeo were investigated for their 2,2-diphenyl-1-picryhydrazyl (DPPH) scavenging activities (IC50 were 7.74 ± 0.47 and 7.91 ± 0.43 µg/mL, respectively). Cellular antioxidant effects in human embryonic kidney-293 (HEK-293) cells with these extracts (0.1 mg/mL) also increased the mRNA expressions of manganese superoxide dismutase (Mn-SOD), glutathione peroxidase 1 (GPx-1), catalase and glutathione reductase (GRe). The leaf extract showed the higher efficacies in the induction of the mRNA expressions of Mn-SOD, GPx-1 and GRe while the stem extract exhibited a stronger effect to the induction of catalase. Phak phaeo in vitro inhibitory effects to α-glucosidase enzyme (IC50 values of 9.82 ± 1.64 and 13.99 ± 1.45 µg/mL, respectively and also strong inhibition to α-amylase with IC50 values of 90.66 ± 8.75 and 19.96 ± 5.37 µg/mL, respectively). Lineweaver-Burk plot demonstrated that phak phaeo extracts inhibited α-glucosidase and α- amylase in non-competitive manners. Total phenolic and total flavonoid contents were determined by Folin-Ciocalteu and aluminium chloride methods (the leaf and stem extracts were 22.89 ± 9.16 and 22.27 ± 8.77 g gallic acid equivalent in 100 g extract (g% GAE) and 7.20 ± 3.61 and 4.06 ± 1.73 g quercetin equivalent in 100 g extract (g% QE), respectively). Keywords: Antioxidant enzymes, DPPH, HEK-293, MTT assay, Persicaria odorata, Reactive oxygen species, Total phenolic, Total flavonoid, α-glucosidases, α-amylase


Author(s):  
Sidra Munir

When the antioxidants in our immune system cannot neutralize or convert Reactive oxygen species into safe molecules at the rate at which it is produced then this imbalance is termed as “oxidative stress”. It is related with a wide array of diseases that includes cancer, diabetes, cardiovascular diseases, hypertension etc. These ROS species however are utmost essential for the proper functioning of human body which are produced as a consequence of partial oxidation of cellular metabolism performing essential functions such as protein phosphorylation, activation of several transcriptional factors, apoptosis, immunity, and differentiation. The sources by which these are produced can be broadly classified are intrinsic and extrinsic sources. There are variety of natural antioxidant enzymes of human body that combat against this oxidative stress. The extrinsic sources of ROS include the use of natural plants, extracted flavonoids and vitamins. In this review we will briefly explain how the sources of ROS, its essential function in human body, its elevation and associated damage to organs and effect on various diseases, and a hope of finding a way of how this oxidative stress can be exploited for therapeutic potential.


Author(s):  
Kwang-Youn Kim ◽  
Tae-Woo Oh ◽  
Hye-Jin Yang ◽  
Young-Woo Kim ◽  
Jin-Yeul Ma ◽  
...  

Abstract Background Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells. Methods Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed. Results ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation. Conclusion These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1672 ◽  
Author(s):  
Yuying Li ◽  
Fang Guo ◽  
Yingying Guan ◽  
Tinggui Chen ◽  
Kaiqing Ma ◽  
...  

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.


Author(s):  
Marta Goschorska ◽  
Izabela Gutowska ◽  
Irena Baranowska-Bosiacka ◽  
Katarzyna Piotrowska ◽  
Emilia Metryka ◽  
...  

It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.


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