Caffeic acid phenethyl ester triggers apoptosis through induction of loss of mitochondrial membrane potential in CCRF-CEM cells
CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death.
Trypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope.
We detected the time- and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells.
This in vitro data by being supported with clinical data may open the way of the potential use of CAPE for the treatment of leukemia.
KeywordsCAPE ALL Apoptosis Mitochondrial membrane potential Cytotoxicity
- Baran Y, Salas A, Senkal CE, Bielawski J, Gunduz U, Obeid LM, Ogretmen B (2007a) Alterations of human longevity assurance gene 1 (LASS1)/sphingosine kinase-1-dependent ceramide generation and metabolism involve in the regulation of imatinib-induced apoptosis and resistance in K562 human chronic myeloid leukemia (CML) cells. J Biol Chem 282(15):10922–10934CrossRefPubMedGoogle Scholar
- Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG, Kim CH (2004) Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J 18:1670–1681CrossRefPubMedGoogle Scholar
- Cossarizza A, Baccarani-Contri M, Kalashnikova G, Franceschi C (1993) A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 197:40–45CrossRefPubMedGoogle Scholar
- Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, Mestre JR, Grunberger D, Sacks PG, Tanabe T, Dannenberg AJ (1999) Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res 59:2347–2352PubMedGoogle Scholar
- Sahin F, Avci CB, Avcu F, Ural AU, Sarper M, Omay SB, Saydam G (2007) Red grape seed extract and its compound resveratrol exert cytotoxic effect to various human cancer lines. Turk J Hematolol 24:102–109Google Scholar