Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors?

Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical pharmacology.

https://www.journal-of-hepatology.eu/article/S0168-8278(01)00153-2/pdf

Agmatine induces apoptosis in rat hepatocyte cultures

The effect of α-difluoromethylornithine (DFMO) on the apoptosis of HC11 mouse mammary epithelial cells was investigated. The involvement of reactive oxygen species (ROS) and Bcl-2 protein in the mechanism of apoptosis induced by ornithine decarboxylase (ODC) inhibition was also assessed. DFMO (0.1, 1 and 5 mM) induced apoptosis of HC11 cells in dose- and time-dependent manner. Apoptosis manifests itself with morphological features like: cell shrinkage, condensation of chromatin, pyknosis and fragmentation of nucleus, followed by secondary necrosis (putrosis). The decrease in the nuclear DNA contents appearing as the hypodiploidal peak sub-G1 in the DNA histogram was not dependent on the presence of prolactin (5 μg/ml) in DFMO-treated cultures. Apoptosis induced by ODC inhibition was associated with a rapid increase in ROS concentration in HC11 cells observed within 1 h after DFMO treatment. The down-regulation of Bcl-2 as a decrease in cell number expressing bcl-2 and a lowered Bcl-2 protein content in cells expressing this protooncogene was also noted. The administration of putrescine (50 μM) lowered the number of early-apoptotic, late-apoptotic and necrotic cells. Moreover, it increased the number of cells expressing bcl-2. In conclusion, the disturbance of cellular polyamine homeostasis by inhibition of their synthesis enhances mammary epithelial cell susceptibility to apoptosis. It may occur in the mammary gland at the end of lactation, when the depletion of circulating lactogenic hormones and activation of intra-mammary apoptogenic factors expression take place.

Inhibition of ornithine decarboxylase by α-difluoromethylornithine induces apoptosis of HC11 mouse mammary epithelial cells

AIM: To investigate the action of apoptosis in occurrence of liver cacinomas in vivo and the biological effect of Solanum lyratum Thumb on BEL-7404 cell line inducing apoptosis in vitro. METHODS: The apoptosis in the liver carcinoma was detected with terminal deoxynucl neotidyl transferase mediated dUTP nick end labelling (TUNEL); the cancer cells cultured in DMED medium were treated with extract of Solanum lyratum Thumb and observed under microscope, and their DNA was assayed by gel electrophoresis. RESULTS: In vivo apoptotic cells in the cancer adjacent tissues inceased; in vitro treatment of liver cancers with extract of Solanum lyratum Thumb could induce the cells to manifest a typical apoptotic morphology. Their DNA was fractured and a characteristic ladder pattern could be found using electrophoresis. CONCLUSION: In vivo the apoptosis of carcinomas was lower; maybe the cells divided quickly and then the cancers occurred. In the cancer adjacent tissues,the apoptosis pricked up, and in vitro Solanum lyratum Thumb could induce the apoptosis of BEL-7404 cells.

Study of apoptosis in human liver cancers.

The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed, and morphological changes due to programmed cell death (apoptosis) were observed in these MGBCP-treated hepatocellular carcinoma cells. These results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.

Induction of apoptotic cell death in human hepatocellular carcinoma SK-HEP-1 cells by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).

Yasushi Hashimoto

Papers

Induction of apoptotic cell death in human hepatocellular carcinoma SK-HEP-1 cells by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).