Anti-Lung Cancer Effects and Related Mechanisms of α-Caryophyllene In Vitro and In Vivo

α-Caryophyllene is a natural condiment and flavoring additive. Herein, we first study the in vivo and in vitro anti-lung cancer efficacy of α-caryophyllene and its potential mechanism. In antitumor activity in vitro, α-caryophyllene exhibited obvious selective cytotoxicity, and its cytotoxicity against lung cancer A549 cells (IC 50 = 22.94 ± 0.56) was superior to the elemene injection (EI, positive control), while its toxicity against normal cell lines was lower (MRC-5: IC 50 = 76.66 ± 2.60 μg/mL, L929: IC 50 = 44.04 ± 0.72 μg/mL). α-Caryophyllene blocked the cell cycle in the G1 phase via reducing cyclin E2-CDK2 and cyclin D3-CDK 4/6 complexes and increasing p21, thereby suppressing A549 cell proliferation. Simultaneously, α-caryophyllene activated the mitochondrial apoptotic pathway through elevating the Bax/Bcl-2 ratio, lowering ΔΨm, releasing Cyt c, activating caspase 9 and caspase 3, and triggering PARP fragmentation. In addition, α-caryophyllene downregulated N-cadherin and MMP-2 levels, thereby preventing the metastasis of A549 cells. In antitumor activity in vivo, α-caryophyllene effectively suppressed transplanted tumor growth by inducing apoptosis of transplanted tumor cells and was superior to the positive control EI. Therefore, α-caryophyllene has outstanding anticancer properties in vitro and in vivo, showing great potential to become a new anticancer drug in the pharmaceutical field.