Metabolomics and Enzymology Unit, Fundamental and Applied Biology Group, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Curr Drug Metab. 2020;21(3):178-185. doi: 10.2174/1389200221666200226123638.
Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.
癌细胞发生细胞周期基因改变或突变,与正常细胞相比增殖速度较快。这些基因的改变导致有丝分裂调控异常,成为肿瘤进展和对许多药物耐药的基础。作用于细胞周期的药物无法阻止该过程,使癌细胞对细胞凋亡或死亡无反应。长春花生物碱和紫杉烷类药物属于这一类,被称为抗有丝分裂剂。微管蛋白在细胞分裂过程中的有丝分裂中起着重要作用,是长春花生物碱和紫杉烷类药物的作用靶点。这些蛋白质本质上是动态的,由α-β-微管蛋白异二聚体组成。β-微管蛋白,特别是βΙΙΙ 同工型,在癌细胞中的表达通常会发生改变。最初,这些药物在癌症治疗中非常有效,但在初始化疗后未能显示出预期的作用。本综述强调了一些重要的靶点及其耐药机制,并提出了一些来自天然来源的有前途的新药,这可能为化疗的发展提供新的方法。