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Background: Leukemia is known to be a common type of cancer mostly affecting children. The standard therapeutic treatment available for leukemia has many drawbacks with serious side effects. Therefore, plant-based chemotherapeutic agents that show less/no toxic side effects might be an efficient way to treat leukemia. Therefore, in this study, we aimed to explore the potential of β-caryophyllene, obtained from various plants sources, and found that it persuades oxidative stress-associated apoptosis during the repression of inflammation and proliferation in MOLT-4 leukemia cancer cells. Materials and Methods: In this study, MOLT-4 cells were incubated with β-caryophyllene (15 and 20 μM) for 24 h and found that β-caryophyllene increased the level of cytotoxicity and reactive oxygen species (ROS) and decreased the level of antioxidants, mitochondrial membrane potential, and apoptotic reaction in MOLT-4 cells. Cell proliferation and apoptosis are important cellular events, and inhibition of cell proliferation along with the generation of proapoptotic marker has been considered as a novel task for treatment of cancer. Results: According to our results, β-caryophyllene induced apoptosis by downregulating the expression of Bcl-2 family of proteins and upregulating the expression of caspases involved in BAX-associated apoptosis in MOLT-4 cells. It also downregulated the expression of biomarkers involved in proliferation (proliferating cell nuclear antigen and cyclin-D1) and inflammation (tumor necrosis factor-α, interleukin-6, nuclear factor-kappa B, and cyclooxygenase-2). Conclusion: In summary, β-caryophyllene potentially induced apoptosis by generating ROS and by inhibiting inflammation and proliferative genes in MOLT-4 leukemia cells. [ABSTRACT FROM AUTHOR]