与肿瘤发生和癌细胞存活相关的药物靶点研究以及具有不同醉茄内酯成分的工程化印度人参提取物的治疗活性
Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions.
作者信息
Cavaleri Franco, Chattopadhyay Sukalpa, Palsule Vrushalee, Kar Pradip Kumar, Chatterjee Ritam
机构信息
Biologic Pharmamedical Research, Surrey, BC, Canada.
Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal, India.
出版信息
Integr Cancer Ther. 2024 Jan-Dec;23:15347354231223499. doi: 10.1177/15347354231223499.
Ashwagandha () has gained worldwide popularity for a multitude of health benefits inclusive of cancer-preventive and curative effects. Despite numerous research data supporting the benefits of this wonder herb, the actual use of ashwagandha for cancer treatment in clinics is limited. The primary reason for this is the inconsistent therapeutic outcome due to highly variable composition and constitution of active ingredients in the plant extract impacting ashwagandha's pharmacology. We investigate here an engineered yield: an ashwagandha extract (Oncowithanib) that has a unique and fixed portion of active ingredients to achieve consistent and effective therapeutic activity. Using the MCF7 cell line, Oncowithanib was studied for its anti-neoplastic efficacy and drug targets associated with cell cycle regulation, translation machinery, and cell survival and apoptosis. Results demonstrate a dose-dependent decline in Oncowithanib-treated MCF7 cell viability and reduced colony-forming ability. Treated cells showed increased cell death as evidenced by enhancement of Caspase 3 enzyme activity and decreased expressions of cell proliferation markers such as Ki67 and Aurora Kinase A. Oncowithanib treatment was also found to be associated with expressional suppression of key cellular kinases such as RSK1, Akt1, and mTOR in MCF7 cells. Our findings indicate that Oncowithanib decreases MCF7 cell survival and propagation, and sheds light on common drug targets that might be good candidates for the development of cancer therapeutics. Further in-depth investigations are required to fully explore the potency and pharmacology of this novel extract. This study also highlights the importance of the standardization of herbal extracts to get consistent therapeutic activity for the disease indication.
南非醉茄()因其众多健康益处,包括防癌和治疗作用,而在全球范围内广受欢迎。尽管有大量研究数据支持这种神奇草药的益处,但南非醉茄在临床癌症治疗中的实际应用却很有限。主要原因是由于植物提取物中活性成分的组成和结构高度可变,影响了南非醉茄的药理学,导致治疗效果不一致。我们在此研究一种经过工程处理的产品:一种具有独特且固定活性成分比例的南非醉茄提取物(癌得安),以实现一致且有效的治疗活性。使用MCF7细胞系,研究了癌得安的抗肿瘤功效以及与细胞周期调控、翻译机制、细胞存活和凋亡相关的药物靶点。结果表明,经癌得安处理的MCF7细胞活力呈剂量依赖性下降,集落形成能力降低。处理后的细胞显示细胞死亡增加,这可通过半胱天冬酶3酶活性增强以及细胞增殖标志物如Ki67和极光激酶A的表达降低来证明。还发现癌得安处理与MCF7细胞中关键细胞激酶如RSK1、Akt1和mTOR的表达抑制有关。我们的研究结果表明,癌得安可降低MCF7细胞的存活和增殖,并揭示了可能成为癌症治疗药物开发良好候选者的常见药物靶点。需要进一步深入研究以充分探索这种新型提取物的效力和药理学。这项研究还强调了草药提取物标准化对于获得针对疾病适应症的一致治疗活性的重要性。