Abstract
Typhonium giganteum Engl. (BaiFuzi) is one of the herbs commonly used in traditional Chinese medicine against cancer. In our previous studies, 37 compounds were identified the SFE-CO2 (supercritical fluid extraction with CO2) extract by GC-MS, including the four major components [β-sitosterol (40.22%), campesterol (18.45%), n-hexadecanoic acid (9.52%) and (Z,Z)-9,12-octadecadienoic acid (8.15%)]. The anti-cancer mechanisms of the SFE-CO2 extract from T. giganteum Engl. tubers have not been reported as yet. In this paper, the molecular mechanisms of the SFE-CO2 extract-mediated apoptosis in SMMC-7721 cells were further examined. SFE-CO2 extract inhibited the growth of SMMC-7721 cells in a time- and dose-dependent manner, arrested the cell cycle in the S phase and G2/M phase, and induced apoptosis. In addition, reactive oxygen species (ROS) increase, reduction of mitochondrial membrane potential, a rise in intracellular calcium levels were found in SMMC-7721 cells after treated with the extract. Western blot analysis showed that the extract caused down-regulation of Bcl-2 expression, and up-regulation of Bax expression. Moreover, caspase-3 and caspase-9 protease activity significantly increased in a dose-dependent manner. Collectively, our results showed that the SFE-CO2 extract from T. giganteum Engl. tubers induces apoptosis in SMMC-7721 cells involving a ROS-mediated mitochondrial signalling pathway.
Highlights
Apoptosis is a form of programmed cell death which occurs through activation of the cell-intrinsic suicide machinery [1] and is a hallmark of the action of many anticancer drugs [2,3,4]
We explored the mechanisms of the SFE-CO2 extract from T. giganteum Engl. tubers-mediated apoptosis in human hepatoma SMMC-7721 cells
When SMMC-7721 cells were treated with 400 μg/mL SFE-CO2 extract, 67.29 ± 5.48% of cells were killed after 48 h
Summary
Apoptosis is a form of programmed cell death which occurs through activation of the cell-intrinsic suicide machinery [1] and is a hallmark of the action of many anticancer drugs [2,3,4]. Mitochondria play a pivotal role during the process of cell apoptosis which involves in a variety of key events, including loss of mitochondrial membrane potential (MMP), mitochondrial swelling and release of apoptotic proteins [5]. Excessive ROS generation can induce redox-signaling pathways, including oxidative stress, a rise in intracellular calcium levels, loss of cell function, cell cycle arrest, and apoptosis [9,10]. Tubers induced apoptosis in SMMC-7721 cells via cell cycle arrest in S phase. The aqueous extract induces apoptosis in MCF-7 cells via cell cycle arrest in S and G2/M phase [19,20]. Tubers-mediated apoptosis in human hepatoma SMMC-7721 cells. The results of this investigation might provide a scientific explanation for the traditional application of this herbal medicine in hepatic cancer therapy
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