In this work we characterized the action of the lysosomotropic agent LeuLeuOMe as a model for defining the role of lysosomal cathepsins in apoptosis. LeuLeuOMe was found to induce lysosomal membrane permeabilization, resulting in release of lysosomal cathepsins that cleave the proapoptotic Bcl-2 family member Bid and degrade the antiapoptotic member Bcl-2, Bcl-xL, or Mcl-1. Since antiapoptotic Bcl-2 family members are often upregulated in cancer, it can be suggested that lysosomal destabilization has a major potential in cancer treatment.
COBISS.SI-ID: 21719335
Expression levels of the cathepsin B (Ctsb) have been positively correlated with mammary tumour progression and metastasis. However, its roles in the hallmark processes of malignant growth remain poorly defined. Mice lacking Ctsb exhibited reduced cell proliferation in mammary carcinomas and their lung metastases. However, cancer cells lacking Ctsb exhibited significantly higher resistance to apoptosis induction by the lysosomotropic agent LeuLeuOMe. This results indicate anin vivo role for Ctsb in promoting cellular anaplasia in mammary cancers and proliferation in lung metastases.
COBISS.SI-ID: 21554983