The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer

Abstract

Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer.

Flupirtine derivatives as potential treatment for the neuronal ceroid lipofuscinoses

“…Caspase‐dependent extrinsic apoptosis is launched via the death receptor pathway, which activates initiator caspase 8, then effector caspase 3. The intrinsic pathway is activated from mitochondria by cell signals via initiator caspase 9, then effector caspase 3 (Fig. ).…”

“…Caspase 8 upregulation is indispensable for the signal transduction cascade via the extrinsic apoptotic pathway (Fig. ) . Caspase 9 is activated by release of cytochrome c from damaged mitochondria through interaction with APAF‐1 followed by activation of caspase 3 .…”

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells

“…Acute dose toxicity of EPI results in myelosuppression, which consequently decreases the red and white blood cells and platelet count in the blood. Additionally, it can cause transient cardiac arrhythmia and changes in the electrocardiogram [ 6 ]. These aforementioned side effects are associated with poor distribution of EPI among the tissues of healthy and cancerous cells.…”

Lysine Decorated Solid Lipid Nanoparticles of Epirubicin for Cancer Targeting and Therapy

“… 22 EPI can reduce the synthesis of DNA and RNA in cancer cells via straight intercalation into base pairs to deter the DNA transcription. 23 EPI used for chemotherapy and retains vital anticancer action in both primary and metastatic cancers including breast, ovarian, lung and gastric cancers, and lymphomas. EPI has a various spatial orientation of the hydroxyl group that caused faster blood removal and reduced side effect of the drug.…”