Polycyclie aromatic hydrocarbons(PAHs) are a group of compounds consisting of two or more fused aromatic rings.Most of them are formed during incomplete combustion of organic materials such as wood ...and fossil fuels,petroleum products,and coal.The composition of PAH mixtures varies with the source and is also affected by selective weathering effects in the environment.PAHs are ubiquitous pollutants frequently found in a variety of environments such as fresh water and marine sediments,the atmosphere,and ice.Due to their widespread distribution,the environmental pollution due to PAHs has aroused global concern.Many PAHs and their epoxides are highly toxic,mutagenic and/or carcinogenic to microorganisms as well as to higher forms of life including humans.The main aim of this review is to provide contemporary information on PAH sources,route of exposure,worldwide emission rate,and adverse effects on humans,especially with reference to cancer.
Breast cancer presents a significant challenge due to its high rates of illness and mortality, necessitating more effective treatment approaches. While traditional treatments offer some benefits, ...they often lack precision in targeting cancer cells and can inadvertently harm healthy tissues. This study aims to investigate the cytotoxic effects and molecular mechanism of 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone (DDR), extracted from Indigofera aspalathoides Vahl, on breast cancer cells (MDA-MB-231). Through various in vitro assays including wound healing, invasion, Western blotting, and immunofluorescence, the impact of DDR on epithelial-mesenchymal transition (EMT) and metastasis was evaluated. Treatment of MDA-MB-231 cells with different DDR concentrations (0-10 µg/mL) resulted in a significant decrease in invasion and migration, accompanied by the downregulation of metastasis-related proteins including VEGF, uPAR, uPA, and MMP-9. DDR treatment also hindered EMT by upregulating E-cadherin and downregulating N-cadherin, Slug, Twist, and Vimentin. Additionally, inhibition of the PI3K/AKT signaling pathway and downregulation of the NF-кB pathway were observed. These findings highlight the potential of DDR as a valuable source of natural compounds with promising anticancer properties, offering opportunities for the development of novel cancer therapies.
Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and ...grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction, cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer.
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•Kaempferol acts as both a chemopreventive and chemotherapeutic.•It acts to ameliorate various disorders, importantly including cancer.•Kaempferol targets various key players involved in cancer development.
Cancer is a leading cause of death worldwide. Cytochrome P450s (P450s) play an important role in the metabolism of endogenous as well as exogenous substances, especially drugs. Moreover, many P450s ...can serve as targets for disease therapy. Increasing reports of epidemiological, diagnostic, and clinical research indicate that P450s are enzymes that play a major part in the formation of cancer, prevention, and metastasis. The purposes of this review are to shed light on the current state of knowledge about the cancer molecular mechanism involving P450s and to summarize the link between the cancer effects and the participation of P450s.
Purpose. Study the effects of 13-cis-retinoic acid (13-RA), a synthetic analogue of a vitamin A used for the treatment of severe acne, on the blood flow in the rat brain using technetium-99m ...hexamethyl propylene amine oxime (99mTc-HMPAO) imaging. Methods. A total of 30 adult male Wistar rats were divided into the control (C), low-dose (L), and high-dose (H) groups. The L and H rats were exposed subcutaneously to 0.3 and 0.5 mg, respectively, of 13-RA per kg of body weight for seven days. Brain blood flow imaging was performed using a gamma camera. Then, a region of interest (ROI) around the brain (target, T), a whole-body region (WB), and a background region (BG) was selected and delimited. The net 99mTc-HMPAO brain counts were calculated as the net target counts, NTC=T−BG/WB−BG in all groups. At the end of the 99mTc-HMPAO brain blood flow imaging, the brain, heart, kidney, lung, and liver were rapidly removed, and their uptake was determined. Brain histopathological analysis was performed using hematoxylin and eosin stains. In addition, the plasma fatty acids were studied using gas chromatography/mass spectrometry. Results. There were highly significant differences between L and H in comparison to C and across the groups. The 99mTc-HMPAO radioactivity in the brain showed increased uptake in a dose-dependent manner. There were also significant changes in the brain tissues and decreased free fatty acids among the groups compared to C. Conclusion. 13-RA increases 99mTcHMPAO brain perfusion, uptake, and function and reduces fatty acids.
BACKGROUND AND PURPOSE Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) pathway is frequently encountered in several human cancers including multiple myeloma ...(MM). Thus, agents that suppress STAT3 phosphorylation have a potential for treatment of MM. In the present report, we investigated whether thymoquinone (TQ), the main component isolated from the medicinal plant Nigella sativa, modulated the STAT3 signalling pathway in MM cells.
EXPERIMENTAL APPROACH The effect of TQ on both constitutive and IL‐6‐induced STAT3 activation, associated protein kinases, STAT3‐regulated gene products involved in proliferation, survival and angiogenesis, cellular proliferation and apoptosis in MM cells, was investigated.
KEY RESULTS We found that TQ inhibited both constitutive and IL‐6‐inducible STAT3 phosphorylation which correlated with the inhibition of c‐Src and JAK2 activation. Vanadate reversed the TQ‐induced down‐regulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that TQ can induce the expression of Src homology‐2 phosphatase 2 that correlated with suppression of STAT3 activation. TQ also down‐regulated the expression of STAT3‐regulated gene products, such as cyclin D1, Bcl‐2, Bcl‐xL, survivin, Mcl‐1 and vascular endothelial growth factor. Finally, TQ induced the accumulation of cells in sub‐G1 phase, inhibited proliferation and induced apoptosis, as indicated by poly ADP ribose polymerase cleavage. TQ also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells.
CONCLUSIONS AND IMPLICATIONS Our study has identified STAT3 signalling as a target of TQ and has thus raised its potential application in the prevention and treatment of MM and other cancers.
Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere ...shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.
Crosstalk between autophagy and senescence.
Polyphenols as Potent Epigenetics Agents for Cancer Rajendran, Peramaiyan; Abdelsalam, Salaheldin Abdelraouf; Renu, Kaviyarasi ...
International journal of molecular sciences,
10/2022, Volume:
23, Issue:
19
Journal Article
Peer reviewed
Open access
Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. ...In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity.
MicroRNA-202 (miR-202) is a member of the highly conserved let-7 family that was discovered in
and recently reported to be involved in cell differentiation and tumor biology. In humans, miR-202 was ...initially identified in the testis where it was suggested to play a role in spermatogenesis. Subsequent research showed that miR-202 is one of the micro-RNAs that are dysregulated in different types of cancer. During the last decade, a large number of investigations has fortified a role for miR-202 in cancer. However, its functions can be double-edged, depending on context they may be tumor suppressive or oncogenic. In this review, we highlight miR-202 as a potential diagnostic biomarker and as a suppressor of tumorigenesis and metastasis in several types of tumors. We link miR-202 expression levels in tumor types to its involved upstream and downstream signaling molecules and highlight its potential roles in carcinogenesis. Three well-known upstream long non-coding-RNAs (lncRNAs); MALAT1, NORAD, and NEAT1 target miR-202 and inhibit its tumor suppressive function thus fueling cancer progression. Studies on the downstream targets of miR-202 revealed PTEN, AKT, and various oncogenes such as metadherin (
),
,
(
2) and Kirsten rat sarcoma virus (
). Interestingly, an upregulated level of miR-202 was shown by most of the studies that estimated its expression level in blood or serum of cancer patients, especially in breast cancer. Reduced expression levels of miR-202 in tumor tissues were found to be associated with progression of different types of cancer. It seems likely that miR-202 is embedded in a complex regulatory network related to the nature and the sensitivity of the tumor type and therapeutic (pre)treatments. Its variable roles in tumorigenesis are mediated in part thought its oncogene effectors. However, the currently available data suggest that the involved signaling pathways determine the anti- or pro-tumorigenic outcomes of miR-202's dysregulation and its value as a diagnostic biomarker.
Millets are cereal grains whose farming dates back thousands of years and have been farmed and consumed by a wide variety of cultures around the world. In recent times, there has been a growing ...interest in millets due to their medicinal characteristics and nutritional advantages. Millets have a substantial nutritional content and can provide a wide range of beneficial health effects. These foods have a relatively low glycemic index in addition to their high levels of dietary fiber, proteins, vitamins, and minerals. In this review, the most recent information regarding the potential effects of millets on the management of diabetes, the health of the heart, antioxidant activity, anti-cancer capacities, and other therapeutic benefits is investigated. In addition, the report provides an in-depth analysis of the current genome resources that are associated with millets, as well as a summary of the key genetic discoveries that have been made. The report also emphasizes the need for further research to maximize the potential of millets through the utilization of genetic resources and breeding techniques to develop high-nutrient-rich and climate-resilient varieties.
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