Abstract
Our previous findings have demonstrated that bee venom (BV) has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB) activity assay. BV (1–5 μg/mL) inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.
Highlights
In a recent study, lung cancer was expected to account for 26% of all female cancer deaths and29% of all male cancer deaths in 2012 [1]
To determine whether the inhibition of cell growth by Bee venom (BV) was due to the induction of apoptotic cell death, we evaluated the changes in the chromatin morphology of cells by using DAPI staining followed by TUNEL staining assays, and the double labeled cells were analyzed by a fluorescence microscope
Our results showed that the expression of death receptors (DRs) such as DR3 and DR6 in A549 lung cancer cell and DR3, DR4 and DR6 in NCI-H460 lung cancer cell were increased
Summary
Lung cancer was expected to account for 26% of all female cancer deaths and. 29% of all male cancer deaths in 2012 [1]. Appropriate chemopreventive compounds reducing or overcoming resistance is a very hopeful strategy for chemotherapy of lung cancer [5]. Our studies have shown that BV inhibits cancer cell growth through the induction of apoptosis of prostate [7] and ovarian cancer cells [8,9]. BV treatment induces both caspase-dependent and caspase- independent apoptotic cell death through the activation of intracellular Ca(2+)-modulated intrinsic death pathway in human bladder cancer cells [10]. There is no information about the effect of BV on death receptors (DRs) mediated apoptosis in human lung cancer cells
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