Pro-apoptotic and anti-proliferative activities of cassane diterpenoids on squamous carcinoma cells: An in vitro and in silico study

Squamous carcinoma of the head and neck is characterized by aberrant apoptosis that prolongs the proliferative capacity of the cells and by uncontrolled cell growth. This study aimed to examine the pro-apoptotic and antiproliferative effects of <i>Caesalpinia pulcherrima</i> cassane diterpenoids on squamous carcinoma cells <i>in vitro</i>. The cytotoxicity of four (4) cassane diterpenoids {Six-cinnamoyl- 7-hydroxyvouacapen-5-ol(1), pulcherrimin A(2), C(3), and E(4)} isolated from C. pulcherrima was determined in squamous carcinoma cell lines (CAL33, FaDu, and Detroit 562) and in non tumorigenic fibroblast cells. The results showed that compounds 1 and 4 had the highest cytotoxic potential, significantly reducing cell viability in all squamous cell lines in a concentration dependent manner. Compounds 1 and 4 may inhibit the proliferation of CAL33 cells by reducing their ability to divide, decreasing PCNA expression, and suppressing migration. Additionally, treatment with compounds 1 and 4 led to an activation of Caspase 3 expression in FaDu cells. Molecular docking analysis revealed strong binding affinities of compounds 1 and 4 to the Caspase 3 receptor, with values of -8.5 and -8.8 kcal/mol, respectively. These results suggest that Pulcherrimin E and 6-cinnamoyl-7-hydroxylvouacapen-5-ol have potential antitumor effects based on their selective cytotoxic effect on squamous carcinoma cells in vitro.