This thesis show that alpinumisoflavone (AIF) or derrone (DR) from unripe fruits of Cudrania tricuspidata could induce cancer cell death with alternative mode. AIF and DR reduced cell viability with dose-dependent manner in A549 human non-small cell lung cancer (NSCLC) cells. Reduced cell viability ...
This thesis show that alpinumisoflavone (AIF) or derrone (DR) from unripe fruits of Cudrania tricuspidata could induce cancer cell death with alternative mode. AIF and DR reduced cell viability with dose-dependent manner in A549 human non-small cell lung cancer (NSCLC) cells. Reduced cell viability is also appeared in H292 human mucoepidermoid pulmonary carcinoma cells, PC3 human prostate cancer cells, and HCT116 human colorectal cells. To determine whether AIF and DR can caused apoptosis, the cleavage of caspase-3 and PARP protein, which are the apoptosis main markers, is verified by western blot. As a result, the protein cleavages were detected at 80 μM of both compounds, but not presented at relatively low concentrations (20- 60 μM). To find the cause of reduced cell viability at 20 to 60 μM concentration section, morphological changes are observed under the microscope. The formation of various vacuoles was appeared, which is autophagosome, single membrane vacuoles and swollen ER or mitochondria-originated vacuoles. Therefore, the hypothesis is formulated that AIF and DR can induce the non-apoptotic cell death with vacuole formation focused on autophagy, methuosis and paraptosis. First, AIF and DR increased autophagic markers but autophagy inhibitors did not affect change of the cell viability in A549 cells after treated by AIF and DR. Second, the methuosis was not provoked by AIF and DR since the vacuoles were not corresponded with FITC-Dextran. Third, AIF and DR could generate paraptosis because the ER tracker was agglomerate and the swollen ER or mitochondria were observed by TEM in A549 cells. Also the JNK and AMPK were activated in short time but ERK had no changed. Collectively, AIF and DR were reduced cell viability in A549 cell. The apoptotic features are appeared at only high concentration and autophagy- and paraptosis-originated (swollen mitochondria or/and ER) vacuoles are showed at low concentration of AIF and DR. The results of our study suggested that AIF and DR induced alternative cell death mode with dose-dependent manner that paraptosis mainly contributed cell death at relatively low concentrations and apoptosis largely affected to reduced cell viability. Taken together, AIF and DR from C. tricuspidata are the novel paraptosis-inducers with natural product-originated chemical structures, and this is valuable as paraptosis activator that can only happened in the cancer cells but not normal cells.
This thesis show that alpinumisoflavone (AIF) or derrone (DR) from unripe fruits of Cudrania tricuspidata could induce cancer cell death with alternative mode. AIF and DR reduced cell viability with dose-dependent manner in A549 human non-small cell lung cancer (NSCLC) cells. Reduced cell viability is also appeared in H292 human mucoepidermoid pulmonary carcinoma cells, PC3 human prostate cancer cells, and HCT116 human colorectal cells. To determine whether AIF and DR can caused apoptosis, the cleavage of caspase-3 and PARP protein, which are the apoptosis main markers, is verified by western blot. As a result, the protein cleavages were detected at 80 μM of both compounds, but not presented at relatively low concentrations (20- 60 μM). To find the cause of reduced cell viability at 20 to 60 μM concentration section, morphological changes are observed under the microscope. The formation of various vacuoles was appeared, which is autophagosome, single membrane vacuoles and swollen ER or mitochondria-originated vacuoles. Therefore, the hypothesis is formulated that AIF and DR can induce the non-apoptotic cell death with vacuole formation focused on autophagy, methuosis and paraptosis. First, AIF and DR increased autophagic markers but autophagy inhibitors did not affect change of the cell viability in A549 cells after treated by AIF and DR. Second, the methuosis was not provoked by AIF and DR since the vacuoles were not corresponded with FITC-Dextran. Third, AIF and DR could generate paraptosis because the ER tracker was agglomerate and the swollen ER or mitochondria were observed by TEM in A549 cells. Also the JNK and AMPK were activated in short time but ERK had no changed. Collectively, AIF and DR were reduced cell viability in A549 cell. The apoptotic features are appeared at only high concentration and autophagy- and paraptosis-originated (swollen mitochondria or/and ER) vacuoles are showed at low concentration of AIF and DR. The results of our study suggested that AIF and DR induced alternative cell death mode with dose-dependent manner that paraptosis mainly contributed cell death at relatively low concentrations and apoptosis largely affected to reduced cell viability. Taken together, AIF and DR from C. tricuspidata are the novel paraptosis-inducers with natural product-originated chemical structures, and this is valuable as paraptosis activator that can only happened in the cancer cells but not normal cells.
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