Apoptosis-inducing Effect of the Hexane Extracts from Three Native Iranian Euphorbia Plants

Abstract

Background: Cancer is one of the most significant causes of death. Plants with anti-cancer effects have shown to eliminate tumor cells by the induction of apoptosis. Objectives: The present study aimed at investigating the apoptotic effects of 3 Euphorbia native species (E. microciadia Boiss, E. osyridea Boiss, and E. heteradenia Jaub. & Sp.). Methods: Cell lines with the strongest sensitivity to the extracts including HeLa for E. microciadia, K562 for E. heteradenia, and Fen for E. osyridea were investigated for the effects of the plants’ hexane extracts on the induction of apoptosis, according to annexin V/propidium iodide staining by flow cytometry. We used real-time PCR to evaluate the changes in expressions of genes related to the intrinsic and extrinsic apoptosis pathways. Results: Flow cytometry results indicated that 50 μg/mL of all the extracts induced apoptosis in more than 60% of treated cells. Administration of the extracts resulted in increased caspase-3 activity for all treated cell lines. Real-time PCR results showed decreased B-cell lymphoma-2 (Bcl-2) and increased Bax and Fas mRNA levels in cells treated with the extracts. The Bax/Bcl-2 ratio in cells treated with 50μg/mL of E. microciadia was 29.25 ± 12.0 (P < 0.05) and for 100 μg/mL of E. heteradenia. and E. osyridea was 30.2 ± 13.0 (P < 0.05) and 22.2 ± 2.4 (P < 0.001), respectively. Conclusions: The studied plants have shown remarkable apoptosis-inducing effects on tumor cell lines by affecting both the extrinsic and intrinsic apoptosis pathways. Additional studies in terms of their beneficial effects as natural sources of potential anti-cancer agents will be necessary.