Abstract

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. sappanextract as an anticancer agent. Thecytotoxicity 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.

Highlights

  • Lung cancer is one of the most dangerous and leading cancer killers globally.[1]

  • Anticancer activity of C. sappan against A549 cells line The anticancer activity of C. sappan ethanol extract against A549 cells line was determined from cytotoxicity effect, capability inducing apoptosis, inhibiting cell cycle phase, and Bax/Bcl[2] ratio

  • The cytotoxicity effect of C. sappan ethanol extract on A549 cells confirmed that C. sappan ethanol extract could inhibit the growth of A549 cells (Figure 1A)

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Summary

Introduction

Lung cancer is one of the most dangerous and leading cancer killers globally.[1]. In 2020, there were 247,270 new cases of lung cancer in the United States, wherein 130,430 and 116,930 cases were from man and women, respectively. There were 140,7230 deaths from lung cancer, in which 76,370 and 64,360 were man and women, respectively.[2] Lung cancer is the 14th leading cause of death in Indonesia. 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. 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. Conclusions: This study demonstrated that C.sappan has the ability to inhibit cancer cell growth by inducing apoptosis and mitochondrial dysfunction in A549 cells

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