β-caryophyllene, a Natural Bicyclic Sesquiterpene, Induces Apoptosis by Inhibiting Inflammation-Associated Proliferation in MOLT-4 Leukemia Cells

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.