The Improving anti-tumour activity with melatonin-stimulated mesenchymal stem cell-derived exosomes in metastatic triple-negative breast cancer

Abstract

The aim of this study is to increase the bioavailability of melatonin on triple-negative breast cancer (TNBC) cells by loading it into exosomes as well as comparing the therapeutic potentials of melatonin and exosome released from human adipose tissue-derived mesenchymal stem cells. TNBC is one of the most malignant tumours with highly invasive and metastatic features. It is characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. TNBC patients can’t benefit from hormonal or trastuzumab-based therapies targeting these receptors. Exosomes are defined as naturally occurring extracellular vesicles. By enabling the transfer of molecules, exosomes play a role in cancer treatment and dynamic intercellular communication between tumour cells and adjacent stromal compartments. The half-maximum inhibitory concentration IC₅₀ values were 30.38 µg/mL, 40.49 µg/mL and
1.5 mM at the co-administered melatonin and exosome, AT-Exo and Mel groups, respectively, for 48 h. The percentage of late-stage apoptotic induction was found to be 6.3%, 4.1% and 4.6% for TNBC exposed to co-administered melatonin and exosome (2.5 mM +100 µg/mL Mel/Exo) for 24 h, 48 h, 72 h, respectively. In conclusion, the coexistence of exosomes and melatonin represents a promising therapeutic tool that can interfere with key molecular processes such as cytotoxicity and apoptosis cascade in TNBC.