Abstract
Recent evidence suggests that cardiac glycosides might be used for the
treatment of cancer. The ornamental shrub Nerium oleander has been
used in traditional medicine for treating several disorders including
cancer, and extracts from the leaves of this plant have already entered
phase I clinical trials. In this communication, we have prepared a
hydroalcoholic extract from the leaves of Nerium oleander (containing
4.75 ± 0.32 % of cardenolides) and have assessed its cytotoxic activity in
A549 lung cancer cells vs. MRC5 nonmalignant lung fibroblasts. The results
showed that the cytotoxicity of the Nerium oleander extract against
the cancer cell line was significantly higher than that against the
nonmalignant cell line, with a potency and selectivity similar to those of
the anticancer drug cisplatin. Pretreatment of A549 cells with the
antioxidants N-acetylcysteine and catalase slightly prevented the
cytotoxicity of the extract, therefore suggesting that the formation of
reactive oxygen species participates in its cytotoxic activity but does not
play a major role. Nerium oleander extract-induced cytotoxicity and
DNA damage (gamma-H2AX focus formation) were slightly higher in cells
lacking BRCA2 (deficient in homologous recombination repair) than in
parental cells; this indicates that the induction of DNA damage may also
play a role in the cytotoxicity of the extract. Nerium oleander
extract induced a marked inhibition of glycolysis (glucose consumption and
lactate production) in A549 cells, comparable to that of the glycolysis
inhibitor dichloroacetate (currently in clinical development for cancer
therapy). Because platinum compounds are widely used in the treatment of
lung cancer, we tested the cytotoxicity of several combinations of cisplatin
with the extract and found a moderate synergism when Nerium oleander
extract was administered after cisplatin but a moderate antagonism when it
was added before cisplatin. Our results suggest that extracts from Nerium
oleander might induce anticancer effects in patients with lung
cancer and support their possible advancement into phase II clinical trials
for the treatment of this type of cancer.
Key words
Nerium oleander
- Apocynaceae - cardiac glycosides - cardiotonic steroids - anticancer