Akrami Sahar, Kordshouli Shirin Omidvar, Tahmasebi Ahmad, Moghadam Ali, Aram Farzaneh, Golestan Ali, Ramezani Amin, Niazi Ali
Institute of Biotechnology, Shiraz University, Shiraz, 7144165186, Iran.
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Complement Med Ther. 2025 Jul 22;25(1):285. doi: 10.1186/s12906-025-04970-3.
Cancer is a deadly and fast-spreading disease that is a growing health problem worldwide due to a lack of comprehensive screening and appropriate medication. However, natural products derived from medicinal plants have gained attention as potential sources of bioactive compounds that selectively remove cancerous lesions and are nontoxic and safe. Pancreatic cancer (PC) is a major therapeutic challenge and is predicted to surpass breast cancer as the third leading cause of cancer death. This study investigated the cytotoxic effects of methanolic extracts from five Iranian medicinal plants, Cuscuta epithymum, Achillea millefolium, Salvia officinalis, Salvia hydrangea, and Teucrium polium, on pancreatic cancer cell lines (MIA PaCa-2 and PaTu8902). Additionally, we examined the changes in the expression of key genes following treatment with C. epithymum extract. The findings revealed that the plant extracts had a dose-dependent effect on the cell viability of the lines, with the C. epithymum extract exhibiting the greatest cytotoxic effect (IC50 values of 85.03 µg/mL for MIA PaCa-2 and 156.57 µg/mL for PaTu 8902). GC‒MS analysis revealed 25 bioactive compounds in C. epithymum, with quinic acid (14.13%), p-vinylphenol (13.22%), and valeraldehyde (11.21%) as the most abundant. The study also investigated the changes in the expression of the STAT4, PIK3CD, EMP1, and RAB11FIP3 genes in MIA PaCa-2 and PaTu 8902 pancreatic cancer cell lines after treatment with the extract from C. epithymum. A correlation was detected between the expression levels of PIK3CD, STAT4, EMP1, and RAB11FIP3 and various concentrations of C. epithymum extract. The results revealed that the extract increased the mRNA levels of STAT4, PIK3CD, and EMP1, whereas RAB11FIP3 was reduced in the treated cells. Accordingly, C. epithymum extract has strong cytotoxic effects on pancreatic cancer cells and influences the expression of key cancer-related genes, suggesting its potential as a therapeutic candidate for PC treatment. Further in vivo studies are recommended to explore its mechanisms of action and clinical applicability.
癌症是一种致命且传播迅速的疾病，由于缺乏全面的筛查和适当的药物治疗，它在全球范围内正成为一个日益严重的健康问题。然而，源自药用植物的天然产物作为生物活性化合物的潜在来源受到了关注，这些化合物能选择性地消除癌性病变，且无毒安全。胰腺癌（PC）是一个重大的治疗挑战，预计将超过乳腺癌成为癌症死亡的第三大主要原因。本研究调查了五种伊朗药用植物——菟丝子（Cuscuta epithymum）、蓍草（Achillea millefolium）、鼠尾草（Salvia officinalis）、绣球鼠尾草（Salvia hydrangea）和绵毛石蚕（Teucrium polium）的甲醇提取物对胰腺癌细胞系（MIA PaCa - 2和PaTu8902）的细胞毒性作用。此外，我们检测了用菟丝子提取物处理后关键基因表达的变化。研究结果表明，植物提取物对这些细胞系的细胞活力具有剂量依赖性影响，其中菟丝子提取物表现出最大的细胞毒性作用（MIA PaCa - 2细胞系的IC50值为85.03 µg/mL，PaTu 8902细胞系的IC50值为156.57 µg/mL）。气相色谱 - 质谱联用（GC - MS）分析显示菟丝子中有25种生物活性化合物，其中奎尼酸（14.13%）、对乙烯基苯酚（13.22%）和戊醛（11.21%）含量最高。该研究还调查了用菟丝子提取物处理后，MIA PaCa - 2和PaTu 8902胰腺癌细胞系中信号转导和转录激活因子4（STAT4）、磷脂酰肌醇 - 4,5 - 二磷酸3 - 激酶催化亚基δ（PIK3CD）、上皮膜蛋白1（EMP1）和RAB11家族相互作用蛋白3（RAB11FIP3）基因表达的变化。检测到PIK3CD、STAT4、EMP1和RAB11FIP3的表达水平与不同浓度的菟丝子提取物之间存在相关性。结果显示，提取物增加了STAT4、PIK3CD和EMP1的mRNA水平，而在处理后的细胞中RAB11FIP3水平降低。因此，菟丝子提取物对胰腺癌细胞具有很强的细胞毒性作用，并影响关键癌症相关基因的表达，表明其作为胰腺癌治疗候选药物的潜力。建议进一步开展体内研究以探索其作用机制和临床适用性。
