Gallium(III) Complex Induces Immunogenic Cell Death Hallmarks for Chemoimmunotherapy

Tumor
metastases account for nearly 90% of cancer-related fatalities.
To tackle this issue, chemotherapeutic agents that induce immunogenic
cell death (ICD) are being investigated as promising candidates for
metastatic cancer treatment. Herein, the chemical synthesis and biological
evaluation of a novel Ga(III) complex with Schiff bases, [Ga((E)-1-((quinolin-8-ylimino)methyl)naphthalen-2-olato)2][Cl], for potential use in combined chemotherapy and immunotherapy
are reported. This compound exhibited broad cytotoxicity against human
breast cancer, pancreatic cancer, cervical cancer cell lines, and
the noncancerous human fibroblast cell line. Mechanistic investigations
revealed that the compound triggers apoptosis and ICD hallmarks, such
as translocation of calreticulin, phosphorylation of eIF2α,
migration of high mobility group protein 1, and release of adenosine
triphosphate. Deeper biological assessment using multicellular tumor
spheroids of cervical cancer cell lines, a solid tumor model, demonstrated
successful eradication at micromolar concentrations. This study presents
one of the few reported Ga(III) complexes capable of inducing immunogenic
cell death.