Dielschneider Rebecca F, Henson Elizabeth S, Gibson Spencer B
Providence University College, Otterburne, MB, Canada.
Research Institute in Oncology and Hematology, CancerCare Manitoba, 675 McDermot Ave., Winnipeg, MB, Canada.
Oxid Med Cell Longev. 2017;2017:3749157. doi: 10.1155/2017/3749157. Epub 2017 Jul 5.
Lysosomes are membrane-bound vesicles that contain hydrolases for the degradation and recycling of essential nutrients to maintain homeostasis within cells. Cancer cells have increased lysosomal function to proliferate, metabolize, and adapt to stressful environments. This has made cancer cells susceptible to lysosomal membrane permeabilization (LMP). There are many factors that mediate LMP such as Bcl-2 family member, p53; sphingosine; and oxidative stress which are often altered in cancer. Upon lysosomal disruption, reactive oxygen species (ROS) levels increase leading to lipid peroxidation, mitochondrial dysfunction, autophagy, and reactive iron. Cathepsins are also released causing degradation of macromolecules and cellular structures. This ultimately kills the cancer cell through different types of cell death (apoptosis, autosis, or ferroptosis). In this review, we will explore the contributions lysosomes play in inducing cell death, how this is regulated by ROS in cancer, and how lysosomotropic agents might be utilized to treat cancers.
溶酶体是膜结合的囊泡，含有水解酶，用于降解和循环利用必需营养物质，以维持细胞内的稳态。癌细胞增强了溶酶体功能，以实现增殖、代谢并适应应激环境。这使得癌细胞易受溶酶体膜通透性增加（LMP）的影响。有许多因素介导LMP，如Bcl-2家族成员、p53、鞘氨醇以及氧化应激，这些在癌症中常常发生改变。溶酶体破坏后，活性氧（ROS）水平升高，导致脂质过氧化、线粒体功能障碍、自噬和活性铁增加。组织蛋白酶也会释放出来，导致大分子和细胞结构的降解。这最终通过不同类型的细胞死亡（凋亡、自噬或铁死亡）杀死癌细胞。在这篇综述中，我们将探讨溶酶体在诱导细胞死亡中所起的作用、癌症中ROS如何对其进行调节，以及溶酶体促渗剂如何用于治疗癌症。
