Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries Research Division, National Research Centre, 33 El Bohouth st.(former El Tahrir st.), P.O 12622, Dokki, Cairo, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City.
Int J Biol Macromol. 2021 Jul 1;182:1590-1601. doi: 10.1016/j.ijbiomac.2021.05.056. Epub 2021 May 17.
Pancreatic cancer is the fourth most lethal cancer type worldwide. Due to multiple levan applications including anticancer activities, studies related to levansucrase production are of interest. To our knowledge, levan effect on pancreatic cancer cells has not been tested previously. In this work, among eighteen bacterial honey isolates, Bacillus subtilis MT453867 showed the highest levan yield (33 g/L) and levansucrase production (8.31 U/mL). One-factor-at-a-time technique increased levansucrase activity by 60% when MgSO was eliminated. The addition of 60 g/L banana peels enhanced the enzyme activity (192 U/mL). Placket Burman design determined the media composition for maximum levan yield (54.8 g/L) and levansucrase production (505 U/mL). The identification of levan was confirmed by thin-layer chromatography, Fourier-Transform Infrared spectrometric analysis, C-nuclear-magnetic resonance, and H-nuclear-magnetic resonance. Both crude and dialyzed levan completely inhibited the pancreatic cancer cell line at 100 ppm with no cytotoxicity on the normal retinal cell line. The LD of crude levan was 4833 mg/kg body weight. Levan had strong antioxidant activity and significantly reduced the expression of CXCR4 and MCM7 genes in pancreatic cancer cells with significant DNA fragmentation. In conclusion, Bacillus subtilis MT453867 levan is a promising adjunct to pancreatic-anticancer agents with both anti-cancer and chemoprotective effects.
胰腺癌是全球第四大致命癌症类型。由于莱凡在抗癌等多个方面的应用，人们对其生产相关的研究很感兴趣。据我们所知，莱凡对胰腺癌的影响尚未得到检验。在这项工作中，在 18 种细菌蜂蜜分离物中，枯草芽孢杆菌 MT453867 表现出最高的莱凡产量（33 g/L）和蔗糖酶产量（8.31 U/mL）。单因素实验表明，当消除硫酸镁时，蔗糖酶活性提高了 60%。添加 60 g/L 的香蕉皮可将酶活性提高（192 U/mL）。Placket Burman 设计确定了最大莱凡产量（54.8 g/L）和蔗糖酶产量（505 U/mL）的培养基组成。通过薄层色谱、傅里叶变换红外光谱分析、C-核磁共振和 H-核磁共振证实了莱凡的存在。粗提和透析莱凡在 100 ppm 时完全抑制了胰腺癌细胞系，对正常视网膜细胞系没有细胞毒性。粗提莱凡的 LD 为 4833 mg/kg 体重。莱凡具有很强的抗氧化活性，可显著降低胰腺癌细胞中 CXCR4 和 MCM7 基因的表达，并伴有明显的 DNA 片段化。总之，枯草芽孢杆菌 MT453867 莱凡有望成为胰腺癌治疗的辅助药物，具有抗癌和化学保护作用。
