Abstract
<p>Polyphenolic compounds present in fruits, vegetables and grains are bioactive molecules which elicit a wide range of responses both in vivo and in vitro. The aim of this study was to investigate whether the soybean isoflavone Equol could induce apoptosis in ovarian cancer cells. In this study, we evaluated molecular events associated with apoptosis induced by Equol and paclitaxel (PTX) in an ovarian cancer cell line SKOV-3. To assess whether growth inhibition was due to apoptosis, flow cytometry, colorimetry experiments, immunoblot analyses through measuring DNA fragmentation, the level of TRAIL,the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-3, -8 and -9 were also performed. Additional markers of apoptosis were also measured like phosphatidylserine externalization and morphological changes. In addition, glycoprotein P (P-gp) activity in SKOV-3 ovarian cancer cell line was also estimated. The experimental results showed that apoptosis was induced by extrinsic pathway triggered by certain TNF family members. Overall results suggested that Equol induces apoptosis in SKOV-3 cells via a TRAIL and caspase 8-dependent pathway whereas paclitaxel leads to smaller apoptotic events when compared to that of Equol.</p>
Highlights
Ovarian cancer is considered as one of the most common cancers and represents the most lethal gynecological cancer
Caspase-3 Activity Assay was from Calbiochem (USA), Human TRAIL, caspase-9 fluorometric assay kit and Z-LEHD-FMK inhibitor, annexin V-biotin apoptosis detection kit, and Apo-BrdU in situ DNA fragmentation assay kit were supplied by BioVision Inc. (USA), caspase-8 assay kit was from Sigma–Aldrich (USA)
The human SKOV-3 cell line used in the experiments was obtained from American Type Culture Collection (ATCC) (USA)
Summary
Ovarian cancer is considered as one of the most common cancers and represents the most lethal gynecological cancer. The biochemical and molecular mechanisms explaining this resistance are not completely known (Coukos and Rubin, 1998). Despite the introduction of new drugs for the treatment of ovarian cancer, the overall survival of patients suffering from this malignancy is far from satisfactory. Novel therapeutic approaches are urgently needed for ovarian carcinoma. Flavonoids are one of the principal plant hormones and are known to possess diverse functional roles including the regulation of plant apoptosis and cell cycle kinetics. Phytoestrogens were originally recognized as plantderived materials with estrogen-like activity and intensive studies revealed protective effects of phytoestrogens on a variety of diseases, such as prostate and breast cancer (Denis et al, 1999, Lee et al, 1991), osteoporosis (Potter et al, 1998) and cardiovascular diseases (Bakhit et al, 1994)
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