Anticancer activity of Caesalpinia sappan by downregulating mitochondrial genes in A549 lung cancer cell line

Background: The standardization and mechanism of action of Caesalpinia sappan as an anticancer agent are still lacking. This study aimed to understand the mechanism of action of C,sappan extract as an anticancer agent. Methods: This study was conducted using the A549 lung cancer cell line to understand the mechanism of action of C. sappan extract as an anticancer agent. The cytotoxicity activity, cell cycle progression, apoptosis, protein-related apoptosis (i.e., BCL-2and BAX protein) assays, and RNA sequencing were performed level were measured. Moreover, the antioxidant activity, total flavonoids, and phenolics of C.sappan were also assessed. Results: C.sappan has strong antioxidant activity (22.14 ± 0.93 ppm) total flavonoid content of (529.3 ± 4.56 mgQE/g), and phenolics content of (923.37 ± 5 mgGAE/g). The C.sappan ethanol extract inhibited cancer cell growth and arrested at G0/G1 phase of cell cycle, inducing apoptosis by increasing BAX/BCL-2 protein ratio in A549 lung cancer cell line. Furthermore, results from RNA sequencing analysis showed that C.sappan ethanol extract caused downregulation of genes acting on mitochondrial function including adenosine triphosphate (ATP) production and respiration. Conclusions: This study demonstrated that C.sappan has the ability to inhibit cancer cell growth by inducing apoptosis and mitochondrial dysfunction in A549 cells.