The Molecular Mechanism of a Complex1-induced Apoptosis in Cancer Cells of the Esophagus

Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109).

Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells.

EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting.

Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity.

This study reported the first use of Complex 1 for treating EC109 cells and demonstrated its superior anticancer activity. Complex 1 triggered apoptosis by significantly increasing reactive oxygen species (ROS) levels. The mechanism involved the downregulation of Bcl-2 and the upregulation of Bax, which resulted in an elevated Bax/Bcl-2 ratio, mitochondrial membrane potential (MMP) disruption, and activation of the caspase cascades. These findings confirmed that mitochondrialmediated apoptosis is the primary pathway for the anticancer effects of Complex 1.

Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.