Medicago sativa Extracts Enhance the Anticancer Efficacy of GEM in PANC-1 Cells through Apoptosis Induction and BAX/BCL-2/CASP3 Expression Modulation.

Q2 Medicine

Asian Pacific Journal of Cancer Prevention Pub Date : 2025-05-01 DOI:10.31557/APJCP.2025.26.5.1689

Nazanin Jamshidi, Negar Jamshidi, Mohammad Zaman, Mahta Chehrehsaz, Farnaz Roshanfarzad, Vahid Chaleshi, Hamid Asadzadeh Aghdaei

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引用次数: 0

Abstract

Introduction: Pancreatic cancer (PC) has a poor prognosis and limited response to therapies. Combinatorial approaches, such as natural product-based therapies, can enhance anticancer efficacy while minimizing side effects. This study evaluated M. sativa's anticancer properties and its potential as adjunctive therapy with Gemcitabine (GEM) to sensitize PANC-1 cells to chemotherapy.

Methods: The antioxidant activity (AA) and total phenolic content (TPC) of M. sativa extracts (Methanol, Ethyl acetate, and water) were assessed using the DPPH radical scavenging assay. Cytotoxic effects on PANC1 and HUVEC cells were also evaluated by utilizing the MTT assay. Then, apoptosis detection was performed by Annexin V/PI-flow cytometry (FC). Besides, the DNA fragmentation analysis was conducted utilizing agarose gel electrophoresis (AGE). Bcl-2, Bax, and CASP3 expression levels in PANC-1 cells using western blot analysis and qRT-PCR.

Results: Herein, DPPH IC50 values for M. sativa extracts (water, MeOH, EtOH) were 76.21, 110.32, and 65.39 μg/ml, respectively. The water extract of M. sativa exhibited the highest TPC (4612.15 ± 119.4 mgGAE/g). The cytotoxicity IC50 values for EtOH M. sativa extract, GEM, and combined GEM with EtOH M. sativa on PANC1 cells were 68.74, 43.53, and 41.22 µg/ml M. sativa + 25 µg/ml GEM, respectively, with no toxicity observed in HUVEC cells. FC analysis revealed that Combining GEM and EtOH M. sativa yielded the highest apoptosis rate (25.6%). Expression changes in Bcl-2, Bax, and CASP3, as well as morphological alterations and DNA fragmentation, indicated apoptotic cell death.

Conclusion: Our findings suggested that combining M.sativa EtOH extracts with GEM may represent a promising strategy for treating PC.

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紫花苜蓿提取物通过诱导凋亡和调节BAX/BCL-2/CASP3表达增强GEM对PANC-1细胞的抗癌作用

胰腺癌（PC）预后差，对治疗的反应有限。组合疗法，如以天然产物为基础的疗法，可以提高抗癌效果，同时最大限度地减少副作用。本研究评估了m.s ativa的抗癌特性及其作为吉西他滨（GEM）辅助治疗使PANC-1细胞对化疗敏感的潜力。方法：采用DPPH自由基清除法测定苜蓿提取物（甲醇、乙酸乙酯和水）的抗氧化活性（AA）和总酚含量（TPC）。利用MTT法还评估了对PANC1和HUVEC细胞的细胞毒性作用。Annexin V/ pi流式细胞术（FC）检测细胞凋亡。此外，利用琼脂糖凝胶电泳（AGE）进行DNA片段化分析。利用western blot和qRT-PCR分析PANC-1细胞中Bcl-2、Bax和CASP3的表达水平。结果：红花提取物（水、MeOH、EtOH）的DPPH IC50值分别为76.21、110.32、65.39 μg/ml。水提物的TPC最高（4612.15±119.4 mgGAE/g）。黄芪提取物、黄芪提取物、黄芪联合黄芪提取物对PANC1细胞的细胞毒性IC50值分别为68.74、43.53、41.22µg/ml黄芪提取物+ 25µg/ml黄芪提取物，对HUVEC细胞无毒性作用。FC分析显示，GEM与EtOH联合用药的细胞凋亡率最高（25.6%）。Bcl-2、Bax和CASP3的表达变化以及形态学改变和DNA断裂提示凋亡细胞死亡。结论：我们的研究结果表明，将芥花EtOH提取物与GEM联合治疗PC可能是一种很有前途的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

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.