Neurotoxin Botulinum Inserts Apoptotic Effects on Certain Cancer Cell Lines Via Neural Niche of Tumors: A Molecular Study

M. Farhadi, M. Jameie, Bahareh Derakhshanmehr, Moghadam Tahmasebi, M. Soleimani, S. B. Jameie
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Abstract

Background: Background: Botulinum toxin A (BtxA) is a powerful neurotoxin reported to be effective as a cancer adjuvant therapy with fewer side effects. Previously we showed the apoptotic effects of BtxA on the GBM cell line (U87-MG). In order to confirm the positive neurotoxicity of BtxA on other cancer cell lines, including SK-OV-3, CHO, MCF-7, and PC-3, the present research has designed.Methods: The cell lines prepared, cultured, and exposed to different concentrations of BtxA for 24 and 48 hours. Using MTT, Annexin V/PI assays and western blotting, cell viability, and apoptosis studied.Results: Our results showed that different BtxA Botox concentrations led to significant cell death in each cell line in a dose-dependent manner (P < 0.001) but did not for PC-3 cells. The results of the Annexin V/PI staining indicated that BtxA induced apoptosis after 24 hours. The 1.45U, 1.75U, and 1.65U of BtxA respectively induced more than 50% apoptosis in MCF 7, SK-OV-3, and CHO cell lines. The results of caspase 3 showed more protein expression in the treated group compares to the control group.Conclusion: BtxA, as a neurotoxin, can insert therapeutic anti-cancer and apoptotic effects on various types of cancerous cells; further studies need to illuminate the possible mechanisms.
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肉毒杆菌毒素通过肿瘤神经小生境对某些癌症细胞系的凋亡作用的分子研究
背景:肉毒毒素A(BtxA)是一种强大的神经毒素,被报道为癌症的辅助治疗,副作用较少。先前我们展示了BtxA对GBM细胞系(U87-MG)的凋亡作用。为了证实BtxA对包括SK-OV-3、CHO、MCF-7和PC-3在内的其他癌症细胞系的阳性神经毒性,本研究设计了BtxA。方法:制备、培养细胞系,并将其暴露于不同浓度的BtxA中24和48小时。使用MTT、膜联蛋白V/PI测定和蛋白质印迹,研究细胞活力和凋亡。结果:我们的结果表明,不同的BtxA肉毒杆菌毒素浓度在每个细胞系中以剂量依赖的方式导致显著的细胞死亡(P<0.001),但在PC-3细胞中没有。Annexin V/PI染色结果表明BtxA在24小时后诱导细胞凋亡。1.45U、1.75U和1.65U的BtxA分别诱导MCF7、SK-OV-3和CHO细胞系50%以上的细胞凋亡。胱天蛋白酶3的结果显示,与对照组相比,治疗组中的蛋白质表达更多。结论:BtxA作为一种神经毒素,对多种癌细胞具有治疗性抗癌和凋亡作用;进一步的研究需要阐明可能的机制。
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审稿时长
4 weeks
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