This study was designed to evaluate the antimutagenic and cancer chemopreventive effect of Trichosanthes kirilowii and to investigate its mechanism of chemoprevention. Therefore, in vitro assays, we investigated antimutagenic effects, induction of quinone reductase activity and inhibitory effects on...
This study was designed to evaluate the antimutagenic and cancer chemopreventive effect of Trichosanthes kirilowii and to investigate its mechanism of chemoprevention. Therefore, in vitro assays, we investigated antimutagenic effects, induction of quinone reductase activity and inhibitory effects on the growth of human cancer cells of Trichosanthes kirilowii, moreover in vivo assays, effects of hepatic drug-metabolizing enzymes of Trichosanthes kirilowii extracts on the liver damage of B(a)P-treated mice. Futhermore, the effects of Trichosanthes kirilowii on cell cycle regulation proteins and a tumor suppressor protein, p53, and inhibition of cyclooxygenase-2 activity that is expressed during inflammatory conditions were examined.
The results are as follows :
1. To determine the antimutagenic effects of Trichosanthes kirilowii by using Ames test, the methanol extract and its fractions of Trichosanthes kirilowii had no effects of mutagenicity alone. But most of the samples showed mutagenicity effects against N - methyl - N'- nitro - N - nitroso- guanidine, 4 - nitroquinone -1-oxide and benzo(a)pyrene. Especially, the hexane and chloroform fractions exhibited very high antimutagenic activity induced by N - methyl - N'- nitro - N - nitrosoguanidine, 4 - nitroquinone -1-oxide and benzo(a)pyrene but other fractions exhibited low antimutatenic effect.
2. To determine in vivo the cancer chemopreventive effect of Trichosanthes kirilowii on the liver damage of B(a)P-treated mice, contents of lipid peroxide and activity of phase I, II enzymes were investigated. The activities of serum asparatate aminotransferase, alanine aminotransferase and the hepatic contents of lipid peroxide, glutathione, cytochrome P 450 and activities of 7-ethoxyresorufine-O- deethylase, glutathione S-transferase, glutathione peroxide, superoxide dismutase, catalase, quinone reductase after B(a)P-treatment were markedly increased. But those levels were significantly decreased by the treatment of Trichosanthes kirilowii methanol extract.
3. To evaluate induction of quinone reductase activity of Trichosanthes kirilowii by using murine hepatoma cells (Hepa 1c1c7 cells), the hexane and chloroform fractions from Trichosanthes kirilowii methanol extract showed inductive effects of quinone reductase, especially, the chloroform fraction exhibited the most inductive effects of quinone reductase. Also, regarding time-dependent induction of quinone reductase after Trichosanthes kirilowii chloroform fraction, this enzyme activity showed the highest at 24 hours.
4. In inhibitory effects of methanol extract and its fractions of Trichosanthes kirilowii against cancer cell lines such as human hepatocellular carcinoma cells (Hep G2), human colon carcinoma cells (HT 29) and human stomach carcinoma cells (SNU-484, SNU-638) were investigated. The methanol extract, the hexane and chloroform fractions of Trichosanthes kirilowii exhibited strong inhibitory effects on the growth of cancer cells but the other fractions showed low effects. Furthermore, they had effect on the cytotoxicity of normal human liver cells (Chang cell) under the same conditions.
5. To investigate inhibitory mechanism on the growth of cancer cells of Trichosanthes kirilowii, the expression of cell cycle regulation proteins and a tumor suppression protein, p53, in human hepatocellular carcinoma cells (Hep G2) were determined. The chloroform fraction of Trichosanthes kirilowii was resulted in significant dose-dependent down-modulation of the proteins expression of cyclin A, cyclin B1, cyclin D1 and cyclin E, but up-regulation of the protein expression p53. Especially, the chloroform fraction of Trichosanthes kirilowii treatment of the cells resulted high down-modulation of the protein expression of cyclin A.
6. To determine antiinflammatory effects of Trichosanthes kirilowii, cyclooxygenase-2 activity of the methanol extract and its fractions of Trichosanthes kirilowii by using bone marrow derived mast cells were investigated. The methanol extract, the hexane and chloroform fractions of Trichosanthes kirilowii exhibited strong inhibitory effects of cyclooxygenase-2 activity, but the other fractions had little effects. Especially, the chloroform fraction of Trichosanthes kirilowii showed the highest inhibitory effects of cyclooxygenase-2 activity.
This study was designed to evaluate the antimutagenic and cancer chemopreventive effect of Trichosanthes kirilowii and to investigate its mechanism of chemoprevention. Therefore, in vitro assays, we investigated antimutagenic effects, induction of quinone reductase activity and inhibitory effects on the growth of human cancer cells of Trichosanthes kirilowii, moreover in vivo assays, effects of hepatic drug-metabolizing enzymes of Trichosanthes kirilowii extracts on the liver damage of B(a)P-treated mice. Futhermore, the effects of Trichosanthes kirilowii on cell cycle regulation proteins and a tumor suppressor protein, p53, and inhibition of cyclooxygenase-2 activity that is expressed during inflammatory conditions were examined.
The results are as follows :
1. To determine the antimutagenic effects of Trichosanthes kirilowii by using Ames test, the methanol extract and its fractions of Trichosanthes kirilowii had no effects of mutagenicity alone. But most of the samples showed mutagenicity effects against N - methyl - N'- nitro - N - nitroso- guanidine, 4 - nitroquinone -1-oxide and benzo(a)pyrene. Especially, the hexane and chloroform fractions exhibited very high antimutagenic activity induced by N - methyl - N'- nitro - N - nitrosoguanidine, 4 - nitroquinone -1-oxide and benzo(a)pyrene but other fractions exhibited low antimutatenic effect.
2. To determine in vivo the cancer chemopreventive effect of Trichosanthes kirilowii on the liver damage of B(a)P-treated mice, contents of lipid peroxide and activity of phase I, II enzymes were investigated. The activities of serum asparatate aminotransferase, alanine aminotransferase and the hepatic contents of lipid peroxide, glutathione, cytochrome P 450 and activities of 7-ethoxyresorufine-O- deethylase, glutathione S-transferase, glutathione peroxide, superoxide dismutase, catalase, quinone reductase after B(a)P-treatment were markedly increased. But those levels were significantly decreased by the treatment of Trichosanthes kirilowii methanol extract.
3. To evaluate induction of quinone reductase activity of Trichosanthes kirilowii by using murine hepatoma cells (Hepa 1c1c7 cells), the hexane and chloroform fractions from Trichosanthes kirilowii methanol extract showed inductive effects of quinone reductase, especially, the chloroform fraction exhibited the most inductive effects of quinone reductase. Also, regarding time-dependent induction of quinone reductase after Trichosanthes kirilowii chloroform fraction, this enzyme activity showed the highest at 24 hours.
4. In inhibitory effects of methanol extract and its fractions of Trichosanthes kirilowii against cancer cell lines such as human hepatocellular carcinoma cells (Hep G2), human colon carcinoma cells (HT 29) and human stomach carcinoma cells (SNU-484, SNU-638) were investigated. The methanol extract, the hexane and chloroform fractions of Trichosanthes kirilowii exhibited strong inhibitory effects on the growth of cancer cells but the other fractions showed low effects. Furthermore, they had effect on the cytotoxicity of normal human liver cells (Chang cell) under the same conditions.
5. To investigate inhibitory mechanism on the growth of cancer cells of Trichosanthes kirilowii, the expression of cell cycle regulation proteins and a tumor suppression protein, p53, in human hepatocellular carcinoma cells (Hep G2) were determined. The chloroform fraction of Trichosanthes kirilowii was resulted in significant dose-dependent down-modulation of the proteins expression of cyclin A, cyclin B1, cyclin D1 and cyclin E, but up-regulation of the protein expression p53. Especially, the chloroform fraction of Trichosanthes kirilowii treatment of the cells resulted high down-modulation of the protein expression of cyclin A.
6. To determine antiinflammatory effects of Trichosanthes kirilowii, cyclooxygenase-2 activity of the methanol extract and its fractions of Trichosanthes kirilowii by using bone marrow derived mast cells were investigated. The methanol extract, the hexane and chloroform fractions of Trichosanthes kirilowii exhibited strong inhibitory effects of cyclooxygenase-2 activity, but the other fractions had little effects. Especially, the chloroform fraction of Trichosanthes kirilowii showed the highest inhibitory effects of cyclooxygenase-2 activity.
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