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ADIL EL HADRI Y COLS. AN. R. ACAD. NAC. FARM.

a previous study reported the cytotoxic activity of a-humulene on
PC-3, A-549, DLD-1 and M4BEU tumor cells through glutathione de-
pletion and reactive oxygen species production (22). Similarly, our
results showed the production of reactive oxygen species in
sesquiterpene sub-subfractions (F1.1.1, F1.2.1) and commercial
compounds: a-humulene and trans-caryophyllene (data not shown).
The ssf F1.2.1 contained trans-caryophyllene (54.23%) as the main
compound and presented less cytotoxicity than ssf F1.1.1 in the three
cell lines tested. In some works, the sesquiterpenes a-humulene and
trans-caryophyllene are the main active compounds responsible for
the anti-inflammatory actions displayed by the essential oil of Cordia
verbenacea (23). However, the in vivo study of a-humulene adminis-
tered orally to mice was rapidly transported to several important tis-
sues and it was found markedly reduced in some possible inactive
mono and di-epoxides (24).

In the present study, the observed variation in cytotoxic activities
of the fractions, subfractions and sub-subfractions, can be explained
by the sensitivity of the cell line studied. The comparaison of results
from all S. officinalis samples indicates that MCF-7 cells are more re-
sistant than HCT-116 cells, whereas RAW264.7 cells are still more sen-
sitive. Furthermore, the comparison of cytotoxic activity data with the
chemical composition of the fractions F1, F2 and F3 of essential oil
S. officinalis showed that 1,8-cineole and ß-thujone were absent in the
first fraction F1 which was highly cytotoxic, and both compounds
were present in the fractions F2 and F3 (10.87%, 67.05% and 20.72%,
49.06% respectively) with less cytotoxic activity. This observation con-
firmed that 1,8-cineole and ß-thujone were not responsible for the cy-
totoxicity of our essential oil in all cell lines studied.

5. CONCLUSION

The sesquiterpenes a-humulene and trans-caryophyllene were
the main compounds of our sub-subfractions from the essential oil
S. officinalis and had the ability to inhibit cancer cell growth. In
addition, these data suggest that more analysis of the pharmacoki-
netic parameters of active compounds are necessary before starting
the clinical trials.

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