Resveratrol-Induced Modulation of Key Genes and DNA Fragmentation in Chronic Myeloid Leukemia Cells.

Q2 Medicine
Laith Alhawamdeh, Belal Almajali, Ali M Atoom, Hanan Kamel M Saad, Razan Madi, Hamid Ali Nagi Al-Jamal
{"title":"Resveratrol-Induced Modulation of Key Genes and DNA Fragmentation in Chronic Myeloid Leukemia Cells.","authors":"Laith Alhawamdeh, Belal Almajali, Ali M Atoom, Hanan Kamel M Saad, Razan Madi, Hamid Ali Nagi Al-Jamal","doi":"10.31557/APJCP.2025.26.3.905","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the BCR-ABL1 fusion gene, which drives the uncontrolled proliferation of myeloid cells. Despite advancements in treatment, resistance to conventional therapies remains a significant challenge. Resveratrol, a natural polyphenol, has garnered attention for its potential therapeutic properties, including its ability to modulate key genes and induce apoptosis in cancer cells. This study investigated the effects of resveratrol on apoptosis, cell cycle regulation, and DNA fragmentation in CML cells.</p><p><strong>Methods: </strong>K562 CML cells were treated with resveratrol, and their effects were analyzed through CCK-8 assay for cell viability, TUNEL assay for DNA fragmentation, and real-time PCR for gene expression. Key apoptotic genes (BCL-2, AIF, BAX) were assessed alongside survival-related genes (CASP3, PGC1α, Cyclin-D1, p53) to evaluate resveratrol's anti-proliferative and pro-apoptotic potential.</p><p><strong>Result: </strong>Resveratrol exhibited a time-dependent reduction in K562 cell viability, with IC₅₀ values decreasing from 282.2 µM at 24 hours to 107.1 µM and 102.4 µM at 48 and 72 hours, respectively. Apoptotic activity, assessed via the TUNEL assay, revealed significant DNA fragmentation in 55 ± 5% of treated cells, while control cells showed no fragmentation. Gene expression analysis demonstrated upregulation of pro-apoptotic genes, including BCL-2, AIF (p < 0.05), BAX (p < 0.01), and VDAC1 (4.5-fold, p < 0.001). Conversely, genes linked to cell survival and metabolism, such as CASP3, PGC1α, NDUFA9, Cyclin-D1, and p53, were slightly downregulated (p < 0.05), highlighting resveratrol's dual role in promoting apoptosis and inhibiting cell survival.</p><p><strong>Conclusion: </strong>These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"26 3","pages":"905-911"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Pacific Journal of Cancer Prevention","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31557/APJCP.2025.26.3.905","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by the BCR-ABL1 fusion gene, which drives the uncontrolled proliferation of myeloid cells. Despite advancements in treatment, resistance to conventional therapies remains a significant challenge. Resveratrol, a natural polyphenol, has garnered attention for its potential therapeutic properties, including its ability to modulate key genes and induce apoptosis in cancer cells. This study investigated the effects of resveratrol on apoptosis, cell cycle regulation, and DNA fragmentation in CML cells.

Methods: K562 CML cells were treated with resveratrol, and their effects were analyzed through CCK-8 assay for cell viability, TUNEL assay for DNA fragmentation, and real-time PCR for gene expression. Key apoptotic genes (BCL-2, AIF, BAX) were assessed alongside survival-related genes (CASP3, PGC1α, Cyclin-D1, p53) to evaluate resveratrol's anti-proliferative and pro-apoptotic potential.

Result: Resveratrol exhibited a time-dependent reduction in K562 cell viability, with IC₅₀ values decreasing from 282.2 µM at 24 hours to 107.1 µM and 102.4 µM at 48 and 72 hours, respectively. Apoptotic activity, assessed via the TUNEL assay, revealed significant DNA fragmentation in 55 ± 5% of treated cells, while control cells showed no fragmentation. Gene expression analysis demonstrated upregulation of pro-apoptotic genes, including BCL-2, AIF (p < 0.05), BAX (p < 0.01), and VDAC1 (4.5-fold, p < 0.001). Conversely, genes linked to cell survival and metabolism, such as CASP3, PGC1α, NDUFA9, Cyclin-D1, and p53, were slightly downregulated (p < 0.05), highlighting resveratrol's dual role in promoting apoptosis and inhibiting cell survival.

Conclusion: These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
2.80
自引率
0.00%
发文量
779
审稿时长
3 months
期刊介绍: Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: -Epidemiology, detection and screening. -Cellular research and bio-markers. -Identification of bio-targets and agents with novel mechanisms of action. -Optimal clinical use of existing anti-cancer agents, including combination therapies. -Radiation and surgery. -Palliative care. -Patient adherence, quality of life, satisfaction. -Health economic evaluations.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信