Carboxyamidotriazole

Head and neck cancer (HNC) is a malignancy characterized by uncontrolled cell growth with increasing incidence rates and heterogeneity. Hyaluronan binding protein 1 (HABP1) is a glycoprotein that acts as a cell surface marker, influencing the immune tumor environment, and is overexpressed in various epithelial tumors. The role of HABP1 in HNC remains to be investigated. Exosome therapy has emerged as a promising treatment that delivers anticancer compounds directly to tumor sites. Coconut milk is considered a valuable therapeutic agent against cancer. Curcumin Analog Isoleucine (CAI) exhibits better solubility, improved antioxidant properties, and greater antimutagenic effects than curcumin. In the study, we emphasized on exosomal delivery of CAI to affect HABP1 signaling for effective cancer therapy.

The study focused on the isolation and characterization of tender coconut milk-derived exosomes. Exosomal formulation was developed by loading tender coconut milk-derived exosomes with CAI (TC EXO+CAI) through the sonication method. Bioaccessibility assessment was executed for the TC EXO+CAI along with the MTT assay, morphology, nucleus shape, colony formation, AO-EtBr assays, western blot, and gene expression analysis.

The bioaccessibility of TC EXO+CAI was greater than that of CAI or curcumin. TC EXO+CAI was cytotoxic to HNC cells at a lower IC50 value, indicating effective CAI delivery by exosomes. It causes cell shrinkage, nuclear condensation, fewer colonies, and an increased number of apoptotic HNC cells. It reduced the expression levels of HABP1 and associated molecules in HNC cells. The uptake of TC EXO+CAI by HNC cells increases the expression of p53 and caspases, which effectively activates the apoptosis mechanism.

TC EXO+CAI exhibits target-specific delivery, which affects tumor cell physiology by reducing HABP1 levels and prompting apoptosis in HNC cells.