Jogi Mukesh, Asnani Hitakshi, Singh Sohini, Kumar Pramod
Division of Molecular Biology, ICMR-National Institute of Cancer Prevention and Research (NICPR), NOIDA, India.
Amity Institute of Biotechnology, Amity University, NOIDA, India.
Mini Rev Med Chem. 2025;25(1):27-41. doi: 10.2174/0113895575293138240527061556.
A significant contributor to cancer-related death, pancreatic cancer (PC) has a terrible prognosis in general that has not altered over many years. Currently, it is extremely difficult to prevent disease or discover it early enough to initiate treatment. PC is a challenging malignancy to treat, and several major impediments significantly impact the effectiveness of its treatment. These obstacles primarily include chemoresistance, drug toxicity, and limited drug bioavailability. Phytochemicals can be used as an alternative to chemotherapeutic drugs, or they can augment the anticancer properties of the chemotherapeutic agents. Nimbolide (NL) is a prominent limonoid compound found in , and has garnered substantial attention as a phytochemical with anticancer potential. It has powerful antiproliferative effects on a variety of cancer cell lines and is effective as a chemotherapeutic in preclinical studies. The primary modes of action of NL include suppression of metastasis and angiogenesis, activation of apoptosis, anti-proliferation, and control of enzymes that metabolize carcinogens. Despite numerous pharmacodynamic (PD) investigations, NL is still in the early stages of the drug development process because no comprehensive pharmacokinetic studies or long-term toxicity studies. Preclinical and toxicological assessments should be conducted to establish an appropriate dosage range, ensuring the safety of NL for its application in initial human clinical trials. This review endeavors to provide a comprehensive summary of the current developmental stage of NL along with nanoparticles as a principal candidate for therapeutic purposes in PC.
胰腺癌（PC）是癌症相关死亡的一个重要原因，总体预后很差，多年来一直没有改变。目前，预防该疾病或尽早发现以便开始治疗极其困难。PC是一种难以治疗的恶性肿瘤，有几个主要障碍严重影响其治疗效果。这些障碍主要包括化疗耐药性、药物毒性和有限的药物生物利用度。植物化学物质可作为化疗药物的替代品，或者增强化疗药物的抗癌特性。Nimbolide（NL）是一种在[具体来源未给出]中发现的著名柠檬苦素类化合物，作为一种具有抗癌潜力的植物化学物质受到了广泛关注。它对多种癌细胞系具有强大的抗增殖作用，并且在临床前研究中作为化疗药物有效。NL的主要作用方式包括抑制转移和血管生成、激活凋亡、抗增殖以及控制代谢致癌物的酶。尽管进行了大量的药效学（PD）研究，但由于没有全面的药代动力学研究或长期毒性研究，NL仍处于药物开发的早期阶段。应该进行临床前和毒理学评估以确定合适的剂量范围，确保NL在最初的人体临床试验中应用的安全性。本综述致力于全面总结NL目前的发展阶段以及纳米颗粒作为PC治疗主要候选药物的情况。
