Bithi Sumaya Akter, Al Hasan Md Sakib, Bhuia Md Shimul, Mia Emon, Yana Noshin Tasnim, Hasan Ali Mohamod Wasaf, Uddin Mohammed Burhan, Sayeed Md Abu, Emon Yasin, Hasan Rubel, Chowdhury Raihan, Islam Muhammad Torequl
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center Ltd, Gopalganj, 8100, Bangladesh.
Med Oncol. 2025 Mar 3;42(4):87. doi: 10.1007/s12032-025-02646-z.
Prunetin (PRU), a naturally occurring flavonoid, has gained recognition for its wide-ranging therapeutic benefits, though its anticancer properties have yet to be extensively reviewed. This study explores the potential of PRU in targeting critical molecular pathways involved in tumor progression, including oxidative stress, apoptosis, cell cycle regulation, and metastasis. Data were compiled from reputable sources, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings emphasize PRU's ability to mitigate oxidative stress, promote apoptosis, and regulate the cell cycle in cancer cells. Its anti-inflammatory and anti-angiogenic properties further enhance its effectiveness against cancer. Mechanistic studies reveal that PRU suppresses oncogenic pathways such as PI3K/Akt/mTOR (Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin) while activating tumor-suppressor mechanisms. Experimental models show that PRU effectively inhibits cancer cell proliferation and metastasis. Additionally, PRU exhibits favorable pharmacokinetics, demonstrating high intestinal absorption (95.5%), good Caco-2 permeability, and metabolism via CYP1A2, CYP2C19, CYP2C9, and CYP3A4, though it has poor blood-brain barrier (BBB) permeability and limited aqueous solubility, posing challenges for systemic bioavailability. Beyond its anticancer properties, PRU displays broad pharmacological relevance, including anti-inflammatory, cardioprotective, neuroprotective, anti-obesity, and osteoprotective effects, mediated through pathways, such as NF-κB, MAPK, and AMPK. Toxicological studies indicate a favorable safety profile, with low cytotoxicity in normal cells and no significant toxicity at high doses in preclinical models. While clinical evidence on PRU remains limited, studies on structurally related isoflavones suggest promising therapeutic potential, necessitating further clinical trials to establish its efficacy and safety in humans.
柚皮素(PRU)是一种天然存在的黄酮类化合物,因其具有广泛的治疗益处而受到认可,不过其抗癌特性尚未得到广泛综述。本研究探讨了PRU在靶向参与肿瘤进展的关键分子途径方面的潜力,这些途径包括氧化应激、细胞凋亡、细胞周期调控和转移。数据来自包括PubMed、Springer Link、Scopus、Wiley Online、Web of Science、ScienceDirect和Google Scholar在内的权威来源。研究结果强调了PRU减轻氧化应激、促进细胞凋亡以及调节癌细胞细胞周期的能力。其抗炎和抗血管生成特性进一步增强了其抗癌效果。机制研究表明,PRU抑制PI3K/Akt/mTOR(磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素哺乳动物靶标)等致癌途径,同时激活肿瘤抑制机制。实验模型表明,PRU有效抑制癌细胞增殖和转移。此外,PRU表现出良好的药代动力学特性,肠道吸收率高(95.5%),Caco-2通透性良好,可通过CYP1A2、CYP2C19、CYP2C9和CYP3A4代谢,不过其血脑屏障(BBB)通透性差,水溶性有限,这对全身生物利用度构成挑战。除了抗癌特性外,PRU还具有广泛的药理学相关性,包括通过NF-κB、MAPK和AMPK等途径介导的抗炎、心脏保护、神经保护、抗肥胖和骨保护作用。毒理学研究表明其安全性良好,在正常细胞中细胞毒性低,在临床前模型中高剂量时无明显毒性。虽然关于PRU的临床证据仍然有限,但对结构相关异黄酮的研究表明其具有有前景的治疗潜力,因此有必要进一步进行临床试验以确定其在人体中的疗效和安全性。