Bee venom inhibits the proliferation and migration of cervical-cancer cells in an HPV E6/E7-dependent manner

Abstract

Bee venom (BV), secreted from the venom gland of the honey bee, contains several biological active compounds. BV has been widely used as a traditional medicine for treating human disease, including cancer. In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose-and time-dependent manner. Interestingly, the killing effect of BV was specific to HPVpositive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and increased the levels of cell-cycle inhibitors, such as p21 and p27. BV significantly induced apoptosis and inhibited wound healing and migration of cervical-cancer cells. It also upregulated the expression of pro-apoptotic BAX and downregulated the expression of anti-apoptotic Bcl-2 and Bcl-XL. Cleavage of caspase-3, caspase-9, and PARP were also induced by BV treatment, whereas the phosphorylation of mitogenic signalingrelated proteins, such as AKT, JNK, p38, and ERK, were downregulated. Our results indicate that BV has a therapeutic selectivity for HPV-positive malignant cells, so further clinical studies are needed to assess its clinical application. [BMB Reports 2020; 53(8): 419-424]

Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice

“…3T3-L1 cells were transfected with mouse galectin-1 siRNA (50 nM) using Lipofectamine RNAiMAX (Invitrogen, Carlsbad, CA, USA), according to the manufacturer's protocol. After 24 h, the medium was replaced with maintenance medium supplemented with 10% calf serum 38,39 .…”

Pharmacological effects and mechanisms of bee venom and its main components: Recent progress and perspective

“…BV demonstrated the ability to inhibit the growth and migration of HPV-positive cervical cancer Caski and HeLa cells, and cell cycle protein Cyclin A and Cyclin B, Akt, JNK and p38/44/42 and their phosphorylated proteins associated with mitogenic signaling pathways were inhibited, and pro-Caspase-3, pro-Caspase-9, cleaved polyadenosine-diphosphate-ribose polymerase (PARP), Bcl-2 and Bcl-xL expression was reduced. On the contrary, proteins such as p53, p21, and retinoblastoma (Rb) were upregulated in expression with the utility of BV, and the number of dead and apoptotic cells was significantly promoted ( Kim D. H. et al, 2020 ). It is worth noting that the main mode of death of HeLa cells after BV treatment is apoptosis, which causes severe cell membrane damage and cell shrinkage ( Borojeni et al, 2020 ), while MEL can show the effect of inhibiting HeLa cell proliferation and inducing apoptosis such as cell shrinkage and structural disorganization ( Zarrinnahad et al, 2018 ).…”

Bee venom protects against pancreatic cancer via inducing cell cycle arrest and apoptosis with suppression of cell migration

“…Notably, melittin and its extract hybrid peptides have demonstrated anti-tumor effects in tumorderived cell lines (23)(24)(25)(26). It has been reported that crude bee venom and melittin exhibited the inhibition capability in several cancer cell lines such as melanoma, colon, breast, and cervical cancer cells (27)(28)(29)(30). Due to the wide range of biological properties, bee venom attracts more and more attention.…”