Tumor Cell Death via Apoptosis and Improvement of Activated Lymphocyte Cytokine Secretion by Extracts from Euphorbia Hebecarpa and Euphorbia Petiolata

Document Type: Research Articles

Authors

1 Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Autoimmune Diseases Research Center, and Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

4 Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

Background: Immunomodulatory materials from natural herbs and the characterization of their immune enhancement
effects may have tremendous potential as cancer treatment. The aim of the present study was to investigate the
apoptosis-inducing activities of Euphorbia hebecarpa Boiss and Euphorbia petiolata Banks & Sol. plant extracts and
their effects on cytokine secretion by lymphocytes. Materials and Methods: We assessed the apoptosis-inducing
effect of the plants’ hexane extracts on previously determined sensitive cell lines (HeLa for E. hebecarpa and K562
for E. petiolata) by flow cytometry and measurement of caspase 3 activation. The apoptosis-related gene expressions
were examined by real-time PCR. The effects of the extracts on lymphocyte proliferation and cytokine secretion were
examined. Results: Flow cytometry analysis showed that the inhibitory effect of the extracts on tumor cell growth
was due to cell apoptosis. The plant extracts at the 100 μg/ml dose induced apoptosis in HeLa (98.5 ± 0.1%) and K562
(57.7 ± 1.9%) cells. The extracts increased caspase 3 activation (≈2-fold>control). Real-time PCR showed Fas and Bax
gene upregulation and Bcl-2 downregulation, which resulted in an increased Bax/Bcl-2 expression ratio. The extracts
increased lymphocyte proliferation and increased levels of IFN-γ production in the presence and absence of mitogen
(p < 0.05). They significantly increased IL-4 and decreased IL-10 secretion by mitogen-stimulated lymphocytes.
E. hebecarpa also increased IL-17 release. Conclusion: These results have shown that both extracts possess antitumor
activity by inducing apoptosis, possibly through both intrinsic and extrinsic pathways. In addition, they induced secretion
of different T helper subset related cytokines that are effective in the immune response against cancer.

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