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Antiproliferative effect of pineal indoles on cultured tumor cell lines
1Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
Abstract:
The in vitro antiproliferative action of pineal indoles on several tumor cell lines including melanoma (B16), sarcoma (S180), macrophage-like cell line (PU5), fibroblasts (3T3), and choriocarcinoma (JAr) was examined by measuring the incorporation of 3H-thymidine by the tumor cells, and, in the case of melanoma cells, by also measuring the incorporation of 3H-leucine and 3H-uridine. Uptake of crystal violet was used to assess the viability of the tumor cells. The order of inhibitory potency of the indoles was found to be methoxytryptamine > melatonin, methoxytryptophol, hydroxytryptophol, and methoxyindoleacetic acid > serotonin and hydroxyindoleacetic acid. The possibility of an adverse effect of the indoles on the viability of normal cells was also investigated by employing a primary culture of rat hepatocytes. The release of glutamate-oxaloacetate transaminase by hepatocytes was not affected by the indoles, although the release of glutamate-pyruvate transaminase was increased to a small extent and the uptake of crystal violet was slightly inhibited.
Insights
Pineal indoles exhibit antiproliferative effects on various cancer cells, with methoxytryptamine being the most potent. These compounds showed minimal adverse effects on normal rat hepatocytes, suggesting potential therapeutic applications.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- The pineal gland produces indoles, which are implicated in various physiological processes.
- Understanding the antiproliferative potential of pineal indoles is crucial for cancer research.
Purpose of the Study:
- To investigate the in vitro antiproliferative activity of pineal indoles against a panel of tumor cell lines.
- To assess the potential toxicity of these indoles on normal cells, specifically rat hepatocytes.
Main Methods:
- Tumor cell lines (melanoma, sarcoma, macrophage, fibroblasts, choriocarcinoma) were treated with pineal indoles.
- Cell proliferation was measured by 3H-thymidine incorporation.
- Cell viability was assessed using crystal violet uptake.
- Hepatocyte cultures were used to evaluate potential toxicity via enzyme release and crystal violet uptake.
Main Results:
- Pineal indoles demonstrated varying degrees of antiproliferative activity across tumor cell lines.
- Methoxytryptamine exhibited the highest inhibitory potency, followed by melatonin and other indoles.
- Indoles showed minimal impact on hepatocyte viability, with slight inhibition of crystal violet uptake and minor increases in glutamate-pyruvate transaminase release.
Conclusions:
- Pineal indoles possess significant in vitro antiproliferative properties against diverse cancer cell types.
- The tested indoles exhibit a favorable safety profile concerning normal liver cells, warranting further investigation for cancer therapy.