Abstract.Several studies have shown that curcumin can induce apoptosis and inhibit growth in human tumor cell lines. However, the mechanism is not completely understood yet. The present studies were designed to investigate the effects of curcumin on human A549 lung adenocarcinoma cells lines to better understand its effect on apoptosis and apoptosis-related genes in vitro. Apoptosis induction, mitochondria membrane potential, mitochondria structure, and apoptotic associated gene expression were examined by flow cytometric assay, confocal microscopy, Western blotting and electron microscopy. After treatment with curcumin, percentage of apoptotic cells increased dose-and timedependently, and morphology observation revealed typical apoptotic features. Our data further indicated that the expression of Bax proteins in A549 cells was increased in a dose-dependent manner, whereas the expression of Bcl-2 was significantly decreased, thus the ratio of Bax/Bcl-2 was increased. The apoptotic process was accompanied by the change of mitochondrial function and structure which led to release of the cytochrome c, and activation of caspase-9 and caspase-3. Furthermore, curcumin also induced a dosedependent cleavage of PARP. Caspases activation during the course of curcumin-induced apoptosis was additionally confirmed by using a broad-spectrum caspases inhibitor, Z-VAD-fmk. As expected, the inhibitor was able to decrease curcumin-induced apoptosis on A549 cells. These results suggested that mitochondria played an important role in the curcumin-induced apoptosis, and mitochondria membrane potential loss initiated apoptosis via the activation of caspases.

Abstract.The mechanism by which trifluoperazine (TFP) induces apoptosis and inhibits growth in human A549 lung adenocarcinoma cells has not been entirely elucidated. In the present study, we investigated the anticancer mechanism of TFP in vitro using the human A549 lung adenocarcinoma cell line. The results indicate that TFP significantly inhibited the proliferation of A549 cells in a dose-and time-dependent manner by inducing apoptosis. Apoptotic progression in A549 cells was associated with the disruption of actin microfilaments. Moreover, the anti-apoptotic Bcl-2 protein and F-actin were down-regulated by TFP treatment, while Bax protein levels were enhanced and the phosphorylation levels of ERK and JNK proteins were increased. The data provide a potential mechanism for the chemopreventive activity of calmodulin antagonist, and suggest that TFP may have therapeutic potential for the treatment of human lung cancer.