Cytoxicity of cinnamic aldehyde on mouse leukemia L1210 cells

Abstract

On screening various oriental hervals which have long been used as medicines to treat some cancer-like diseases we have found in our laboratory that water extracts of the bark of $\mbox{\underline{Cinnamomum}}$ $\mbox{\underline{cassia}}$ have strong inhibitory effect on mouse leukemia L1210 cells. Later, the active substance contained in the extracts was found to be cinnamic aldehyde (CA) which is the main component of cinnamon oil. The present investigation was planned to clarify the mechanisms involved in the inhibition of CA on the growth of the L1210 cells. The mouse leukemic cells were grown in the Fischer``s medium fortified with horse serum under the presence or absence of CA for 48 hours and the effect of CA on the cell growth was observed. Similarly, cinnamic acid and cinnamic alcohol, both of which have molecular structures similar to that of CA have also been tested to find the active site of CA molecule. Utilization of glucose as well as formation of lactate during the growth of L1210 cells were checked to see the effect of CA on the glycolysis of the cells. For the inhibitory effect on macromolecular synthesis the isotope technique was employed. That is, the use of [$^3H$]-thymidine for incorporation into DNA,[$^3H$]-uridine for incorporation into RNA, and [$^3H$]-leucine for incorporation into protein molecules. To confirm the reaction between CHO-group of CA and SH-group of cell components the total SH-groups in culture solution treated with CA were determined. Additions of cysteine and glutathione as sources of SH-groups into CA containing buffer solution were attempted. Treatment of CA with cysteine before addition to culture broth was also tried to prevent CA-inhibition which is another proof of direct reaction between the two active groups, CHO of CA and SH of cysteine. A continuous culture of L1210 cells in a chemostat having working volume of 420 ml was also tried in order to establish a unique culture method suitable for studying adaptati...