Department of Medical Biology, Jan Kochanowski University in Kielce, 25-406 Kielce, Poland.
Int J Mol Sci. 2023 Jan 22;24(3):2176. doi: 10.3390/ijms24032176.
Lysosomes are organelles containing acidic hydrolases that are responsible for lysosomal degradation and the maintenance of cellular homeostasis. They play an important role in autophagy, as well as in various cell death pathways, such as lysosomal and apoptotic death. Various agents, including drugs, can induce lysosomal membrane permeability, resulting in the translocation of acidic hydrolases into the cytoplasm, which promotes lysosomal-mediated death. This type of death may be of great importance in anti-cancer therapy, as both cancer cells with disturbed pathways leading to apoptosis and drug-resistant cells can undergo it. Important compounds that damage the lysosomal membrane include lysosomotropic compounds, antihistamines, immunosuppressants, DNA-damaging drugs, chemotherapeutics, photosensitizers and various plant compounds. An interesting approach in the treatment of cancer and the search for ways to overcome the chemoresistance of cancer cells may also be combining lysosomotropic compounds with targeted modulators of autophagy to induce cell death. These compounds may be an alternative in oncological treatment, and lysosomes may become a promising therapeutic target for many diseases, including cancer. Understanding the functional relationships between autophagy and apoptosis and the possibilities of their regulation, both in relation to normal and cancer cells, can be used to develop new and more effective anticancer therapies.
溶酶体是含有酸性水解酶的细胞器，负责溶酶体降解和细胞内稳态的维持。它们在自噬以及各种细胞死亡途径中发挥重要作用，如溶酶体和凋亡性死亡。各种试剂，包括药物，可以诱导溶酶体膜通透性增加，导致酸性水解酶转移到细胞质中，从而促进溶酶体介导的死亡。这种类型的死亡在癌症治疗中可能非常重要，因为具有紊乱的凋亡途径的癌细胞和耐药细胞都可能发生这种死亡。破坏溶酶体膜的重要化合物包括溶酶体靶向化合物、抗组胺药、免疫抑制剂、DNA 损伤药物、化疗药物、光敏剂和各种植物化合物。用溶酶体靶向化合物与自噬的靶向调节剂联合诱导细胞死亡，可能是治疗癌症和寻找克服癌细胞耐药性方法的一个有趣方法。这些化合物可能是肿瘤治疗的一种替代方法，溶酶体可能成为许多疾病（包括癌症）的有前途的治疗靶点。了解自噬和凋亡之间的功能关系以及它们在正常和癌细胞中的调节可能性，可用于开发新的、更有效的抗癌疗法。
