Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER‐signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin‐induced ER stress not only upregulated of glucose‐regulated protein 78/94 and IRE1‐ASK1‐JNK pathway but also leading to calpains and Bcl‐2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase‐9 and caspase‐3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress‐associated IRE1‐ASK1‐JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.
Lysosomes are membrane-bound vesicles that play roles in the degradation and recycling of cellular waste and homeostasis maintenance within cells. False alterations of lysosomal functions can lead to broad detrimental effects and cause various diseases, including cancers. Cancer cells that are rapidly proliferative and invasive are highly dependent on effective lysosomal function. Malignant melanoma is the most lethal form of skin cancer, with high metastasis characteristics, drug resistance, and aggressiveness. It is critical to understand the role of lysosomes in melanoma pathogenesis in order to improve the outcomes of melanoma patients. In this mini-review, we compile our current knowledge of lysosomes’ role in tumorigenesis, progression, therapy resistance, and the current treatment strategies related to lysosomes in melanoma.
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