Anticarcinogenic effects of PPAR ligands on DMBA-induced tumors in rats.
Journal name: World Journal of Pharmaceutical Research
Original article title: Evaluation of the anticarcinogenic effect of some peroxisome proliferator activated receptor ligands on dimethylbenz (î±) anthracene induced mammary tumor in female rats
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Remonda E. Rizk, Wessam F. El-Hadidy, Malak A. Zoheir, Nesrine S. Ibrahim
World Journal of Pharmaceutical Research:
(An ISO 9001:2015 Certified International Journal)
Full text available for: Evaluation of the anticarcinogenic effect of some peroxisome proliferator activated receptor ligands on dimethylbenz (î±) anthracene induced mammary tumor in female rats
Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research
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Summary of article contents:
Introduction
Breast cancer remains the leading cause of cancer-related deaths among women globally, with various risk factors linked to either excessive estrogen exposure or genomic instability. Traditional treatments, including surgery and chemotherapy, face challenges such as resistance and collateral damage to healthy cells. Recent research highlights the potential of nuclear receptors, specifically the peroxisome proliferator-activated receptors (PPARs), in breast cancer biology. This study investigates the anticancer properties of PPAR ligands—fenofibrate, pioglitazone, and omega-3 fatty acids—on 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in female rats, aiming to elucidate their mechanisms of action.
The Role of PPAR Agonists
The study focused on three PPAR agonists: fenofibrate (PPARα ligand), pioglitazone (PPARγ ligand), and omega-3 fatty acids (dual PPARα and γ ligands). These compounds were examined for their effects on tumor growth and proliferation. The results revealed that treatment with any of the agonists significantly reduced tumor volume compared to untreated controls. The most pronounced effect was observed in the omega-3-treated group, suggesting its superior efficacy. The mechanisms through which these agents exert their effects include antiangiogenic, pro-apoptotic, and antiproliferative activities that disrupt key pathways involved in tumor growth.
Impact on Vascular Endothelial Growth Factor (VEGF)
VEGF plays a crucial role in angiogenesis, which is vital for tumor growth. In this study, serum and tumor tissue levels of VEGF were markedly elevated in untreated mice bearing DMBA-induced tumors. However, treatment with PPAR ligands resulted in a significant reduction of VEGF levels in both serum and tumor tissues. The reduction in VEGF suggests an inhibition of angiogenesis, which is key to preventing tumor progression. This finding aligns with existing literature confirming that PPAR ligands can downregulate proangiogenic factors and enhance the expression of angiogenesis inhibitors.
Cyclooxygenase-2 (COX-2) and Apoptosis
COX-2 is an enzyme involved in inflammation and tumor progression, and its levels were found to be lower in tumor samples from treated rats compared to untreated controls. The PPAR agonists also increased levels of caspase-3, a marker of apoptosis, indicating their ability to promote programmed cell death in tumor cells. The suppression of COX-2 activity alongside enhanced apoptosis underscores the potential of these PPAR ligands to alter the tumor microenvironment favorably, contributing to better cancer outcomes.
Conclusion
The findings from this research suggest that PPAR agonists—fenofibrate, pioglitazone, and omega-3—offer promising, non-toxic therapeutic avenues for treating breast cancer. By interplaying with various signaling pathways, these agents demonstrate direct antitumor effects while also promoting apoptosis, inhibiting angiogenesis, and reducing inflammation. As a result, PPAR ligands are strong candidates for further clinical exploration as adjunct therapies in breast cancer management, potentially enhancing the efficacy of conventional treatments.
FAQ section (important questions/answers):
What are PPAR ligands and their role in breast cancer?
PPAR ligands are compounds that activate peroxisome proliferator-activated receptors. They regulate various cellular processes and may provide alternative therapies by exerting anti-tumoral effects, influencing growth factors, and modulating inflammation in breast cancer.
What was the aim of the study conducted by El-Hadidy et al.?
The study aimed to compare the effects of fenofibrate, pioglitazone, and omega-3 on DMBA-induced mammary carcinoma in female rats, exploring their potential anticancer mechanisms and therapeutic benefits.
How was mammary carcinoma induced in the study rats?
Mammary carcinoma was induced in the rats by administering a single dose of 20 mg DMBA suspended in sesame oil, leading to tumor development within 24 to 48 weeks.
What treatment groups were established in this study?
Rats were divided into five groups: untreated controls, fenofibrate-treated, pioglitazone-treated, and omega-3-treated, with each drug administered orally for 28 days.
What were the key findings related to tumor growth?
Untreated rats showed increased tumor growth, while treated groups experienced significant reductions in tumor volume, indicating the effectiveness of PPAR ligands in inhibiting mammary tumor progression.
What conclusions can be drawn from the study results?
The study suggests that PPAR agonists like fenofibrate, pioglitazone, and omega-3 may serve as promising therapeutic agents for breast cancer due to their antiangiogenic, antiproliferative, and pro-apoptotic properties.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “Anticarcinogenic effects of PPAR ligands on DMBA-induced tumors in rats.”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Cancer:
Cancer is a disease characterized by uncontrolled cell division, leading to the formation of tumors. In this study, breast cancer is a focal point, addressing its mechanism of development induced by DMBA and evaluating the effects of various PPAR ligands on tumor growth, progression, and associated signaling pathways.
2) Animal:
The study utilized female Wistar albino rats as a model for investigating the effects of PPAR ligands on mammary tumor development. Animal models are essential in cancer research as they allow for controlled experiments to elucidate the potential therapeutic effects and mechanisms of action of compounds being studied.
3) Study (Studying):
This research study aims to evaluate the anticancer effects of PPAR ligands fenofibrate, pioglitazone, and omega-3 on DMBA-induced mammary carcinomas in rats. The study design involved controlled treatments, while parameters such as tumor volume, growth factors, and histopathological markers were analyzed for comprehensive understanding.
4) Activity:
Activity in this context refers to the biological effects and mechanisms triggered by PPAR ligands, including their antitumor, anti-inflammatory, and pro-apoptotic behaviors. Understanding these activities is crucial for developing effective cancer treatments that can selectively target tumor cells while minimizing harm to healthy tissues.
5) Science (Scientific):
The study exemplifies the application of scientific principles in pharmacology and oncology. It utilizes experimental methods to gather data about the effects of specific compounds on breast cancer, contributing to scientific knowledge aimed at finding effective treatments and improving patient outcomes in cancer therapy.
6) Egypt:
The research was conducted at the Medical Research Institute of Alexandria University, Egypt, emphasizing the role of Egyptian institutions in advancing medical research. This highlights the global contribution to cancer research and the significance of local efforts to address health issues prevalent in the region.
7) Table:
Table refers to the structured presentation of data in the study, summarizing findings such as serum and tumor tissue levels of VEGF, COX-2, and caspase-3. Tables facilitate comparison and help to communicate complex data clearly, enabling easier interpretation of results.
8) Drug:
Drugs like fenofibrate, pioglitazone, and omega-3 are central to the study's investigation. They serve as PPAR ligands with potential therapeutic effects against breast cancer, highlighting the significance of pharmacological agents in altering disease progression and offering insights into new treatment possibilities.
9) Inflammation:
Inflammation is a significant factor in cancer progression, often contributing to the tumor microenvironment. The study explores how PPAR ligands can impact inflammatory pathways, potentially reducing tumor growth and improving outcomes, thereby highlighting the interconnectedness of cancer and inflammatory processes.
10) Relative:
Relative comparisons are made throughout the study to assess the effects of treatments on tumor growth and other evaluated parameters. Understanding relative changes in tumor volume and other measures offers insights into the efficacy of different therapeutic interventions for breast cancer.
11) Line:
Line in this context can refer to line graphs used to visualize changes over time, such as tumor growth relative to different treatment groups. Graphs enhance the clarity of results and facilitate the understanding of trends observed during the course of the study.
12) Pharmacology:
Pharmacology is the branch of medicine that studies drugs and their effects on biological systems. This study contributes to pharmacology by investigating the actions of specific compounds in a cancer model, providing valuable information for the development of future therapies.
13) Chemotherapy:
Chemotherapy traditionally targets rapidly dividing cells, including cancerous tissue; however, it can also affect healthy cells, leading to toxicity. The study seeks alternative therapies, like PPAR ligands, that may offer effective cancer treatment with fewer side effects than conventional chemotherapy.
14) Water:
Water is essential for animal care in experimental setups. All animals have free access to water, which is vital for maintaining hydration and overall health, ensuring that the observed effects of any treatments can be specifically attributed to the administered drugs, not confounding variables.
15) Death:
Death refers to the ultimate consequence of advanced cancer cases. The study aims to identify effective treatments that could potentially reduce mortality from breast cancer by investigating how PPAR agonists can inhibit tumor progression and enhance apoptotic processes.
16) Blood:
Blood samples were collected in the study to assess serum levels of various markers, such as VEGF. Analyzing blood provides critical insights into systemic responses to treatments and allows for the correlation of serum biomarkers with tumor activity and progression.
17) Cage (Cāge):
Cages were used for housing the Wistar albino rats during the study. Proper housing is crucial for maintaining the well-being of the animals, which impacts the validity of the experimental results by reducing stress that could otherwise affect physiological outcomes.
18) Transformation (Transform, Transforming):
Transformation in this context refers to the conversion of normal cells into cancerous cells due to mutagens like DMBA, which can cause genetic mutations. Understanding this process is essential for developing strategies to prevent or reverse cancerous changes through therapeutic interventions.
19) Accumulation (Accumulating, Accumulate):
Accumulation refers to the buildup of specific proteins or factors such as VEGF in tumor tissue, which can influence tumor growth and angiogenesis. Studying these accumulation patterns helps uncover the metabolic changes in cancerous cells and their microenvironment.
20) Discussion:
Discussion is a vital part of research articles where authors interpret the findings, exploring implications, contradictions, and future directions. It highlights key takeaways from the study, discussing how PPAR ligand treatments may pave the way for novel breast cancer therapies.
21) Collecting:
Collecting samples, including blood and tumor tissues, is a fundamental aspect of the study, as it forms the basis for comparative analyses. Proper collection techniques ensure that the data obtained is reliable and can be used to draw valid conclusions.
22) Toxicity:
Toxicity refers to harmful side effects produced by cancer treatments, particularly chemotherapy. The study emphasizes the significance of finding alternative therapies like PPAR ligands that exhibit lower toxicity while effectively targeting cancerous cells compared to traditional treatments.
23) Mutation:
Mutation is a fundamental concept in cancer biology, often referring to genetic changes that can lead to cancer development. The role of mutagens like DMBA is investigated in the study, elucidating how they initiate the carcinogenic process and how interventions can mitigate these effects.
24) Dividing:
Dividing describes the process of cell proliferation, which is a hallmark of cancerous growth. The study evaluates treatments that inhibit the dividing processes of tumor cells, making it a critical focus in the search for effective cancer therapies.
25) Disease:
Disease in this context primarily refers to breast cancer, which is the subject of the study. Understanding its mechanisms and therapeutic targets is essential for developing strategies aimed at prevention, management, and improving survival rates.
26) Family:
Family refers to the biological classification of organisms. In the context of this study, it could denote the broader classification of the compounds used (e.g., drugs) or the genetic similarities shared within certain biological processes, like tumorigenesis.
27) Arrow:
Arrow can refer to the graphical representation of results, including upward or downward trends within graphs. In the context of this study, arrows may symbolize positive or negative changes in tumor parameters in response to treatments, aiding visual comprehension of findings.
28) Beta (Bēṭa, Beṭa):
Beta is often associated with beta-oxidation, a metabolic process for fatty acid breakdown. This concept may apply to the actions of fenofibrate, highlighting its effects on cellular metabolism within the context of inhibiting tumor growth, therefore being relevant to the study.
29) Food:
Food refers to the nutritional intake essential for animal models used in the study. Proper nutrition is integral to the health and metabolism of the rats, ensuring that the observed effects from treatments are not confounded by differences in nutritional status.
30) Hand:
Hand can indicate the manual skills involved in various procedures during the experimental process, from administering drugs to collecting biological samples. This emphasizes the importance of precision and care in conducting experiments to secure valid results.
31) Post:
Post refers to the stage following treatment in the study, particularly when assessing the effects of interventions on tumor growth and biological markers. Post-treatment analyses are critical for evaluating treatment efficacy and safety outcomes.
Other Science Concepts:
Discover the significance of concepts within the article: ‘Anticarcinogenic effects of PPAR ligands on DMBA-induced tumors in rats.’. Further sources in the context of Science might help you critically compare this page with similair documents:
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