Laboratory of AgroBiotechnology and Nutrition in Semi Arid Zones, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria.
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh.
Chem Biol Interact. 2024 Oct 1;402:111218. doi: 10.1016/j.cbi.2024.111218. Epub 2024 Aug 28.
This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.
本文旨在总结生物碱作为潜在的 PI3K/Akt/mTOR（PAMT）通路调节剂在癌症治疗中的作用。PAMT 通路在细胞生长、存活和代谢中发挥着关键作用，其失调导致了癌症的标志性特征。在健康细胞中，该通路受到严格控制。然而，在癌症中，该通路经常失调并变得异常活跃。这种情况可能是由于该通路本身的基因突变或其他因素引起的。这种慢性过度活跃促进了癌症的标志性特征，如不受控制的细胞分裂、抵抗细胞死亡以及增加血管形成以滋养肿瘤。因此，PAMT 通路是癌症的一个重要治疗靶点。研究人员正在开发专门针对该通路不同成分的药物，旨在关闭该通路并减缓癌症的进展。生物碱是一类存在于植物中的天然含氮分子，已成为有潜力的治疗剂。这些生物碱可以靶向 PAMT 通路的不同点，抑制其活性，从而导致癌细胞死亡或抑制肿瘤生长。目前正在研究各种生物碱在癌症治疗中的作用。小檗碱通过靶向 PAMT 通路，降低 mTOR 活性和增加细胞凋亡，抑制癌细胞增殖。石蒜碱抑制 Akt 磷酸化和 mTOR 激活，增加促凋亡蛋白的产生并降低细胞活力。在神经胶质瘤模型中，哈尔明抑制 mTORC1。本文重点介绍了一些生物碱，如吴茱萸碱、荜澄茄碱、钩吻素 J、吲哚-3-甲醇、罂粟碱、小檗碱、胡椒碱等，它们在靶向 PAMT 通路方面显示出了潜力。正在进行评估生物碱作为癌症治疗一部分的临床试验，正在研究它们对患者结局的潜在影响。总之，生物碱代表了一种有前途的靶向癌症失调的 PAMT 通路的方法，需要进一步的研究。
