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  • br In summary the present study demonstrated that

    2020-08-18


    In summary, the present study demonstrated that a first-of-a-kind biologic miR-1291 prodrug was effective as Gem-nP in the control of PC tumor growth in PANC-1 xenograft and different PDX mouse models, while combination therapy with miR-1291 and Gem-nP suppressed xenograft tumor growth to the greatest degrees. Furthermore, all treatments were well tolerated in mice without any signs of hepatic and renal toxicity. Optimal efficacy of combination treatment was attribu-table to the enhanced induction of apoptosis, DNA damage, and mitotic arrest. In addition, the induction of apoptosis by miR-1291 was asso-ciated with upregulation of ARID3B. These results suggest that biologic miR-1291 prodrug may be developed as a new antitumor agent for the treatment of PC, and co-administration of miR-1291 may augment the
    efficacy of current standard chemotherapy Gem-nP.
    Authors' contributions
    Writing, review, and/or revision of the manuscript: M.-J. Tu, A.-M.
    Conflicts of interest
    No potential conflicts of interest were disclosed.
    Acknowledgements
    This study was supported by the grant (U01CA175315 to A.-M. Yu) from the National Cancer Institute and in part by the grant (R01GM113888 to A.-M. Yu) from the National Institute of General Medical Sciences, National Institutes of Health, as well as the 111 project (Grant: B16047) and the National Key Research and Development Program (Grant: 2017YFE0109900 to H. Bi). The authors appreciate the access to the shared resources funded by the UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30CA093373).
    Appendix A. Supplementary data
    References
    [13] A.M. Yu, Y. Tian, M.J. Tu, P.Y. Ho, J.L. Jilek, MicroRNA pharmacoepigenetics: posttranscriptional regulation mechanisms behind variable drug disposition and strategy to develop more effective therapy, Drug Metab. Dispos. 44 (2016)
    X. Chen, miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma, Oncol. Rep. 34 (2015) 2665–2673.
    S. Zeng, M. Huang, A.M. Yu, Chimeric MicroRNA-1291 biosynthesized efficiently in Escherichia coli is effective to reduce target gene expression in human carcinoma aminonucleoside and improve chemosensitivity, Drug Metab. Dispos. 43 (2015) 1129–1136. [23] P.Y. Ho, A.M. Yu, Bioengineering of noncoding RNAs for research agents and therapeutics, Wiley Interdiscip. Rev. RNA 7 (2016) 186–197.
    R. Berjian, H. Douglass, E.W. Martin, T. Chu, Human pancreatic adenocarcinoma: in vitro and in vivo morphology of a new tumor line established from ascites, In Vitro 18 (1982) 24–34.
    [35] D. Delitto, K. Pham, A.C. Vlada, G.A. Sarosi, R.M. Thomas, K.E. Behrns, C. Liu, S.J. Hughes, S.M. Wallet, J.G. Trevino, Patient-derived xenograft models for pan-creatic adenocarcinoma demonstrate retention of tumor morphology through in-corporation of murine stromal elements, Am. J. Pathol. 185 (2015) 1297–1303. [36] M.T. Yip-Schneider, C.J. Sweeney, S.-H. Jung, P.L. Crowell, M.S. Marshall, Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth in-hibition in combination with gemcitabine in pancreatic carcinoma cells, J.
    [40] K. Kobayashi, T. Era, A. Takebe, L.M. Jakt, S. Nishikawa, ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma, Cancer Res. 66 (2006) 8331–8336.
    Contents lists available at ScienceDirect
    Materials Science & Engineering C
    journal homepage: www.elsevier.com/locate/msec
    Bioengineered silver nanoparticles capped with bovine serum albumin and T its anticancer and apoptotic activity against breast, bone and intestinal colon cancer cell lines
    Shahnaz Majeeda, , Farah Hanani Binti Aripina, Nur Syafiqah Binti Shoeba, Mohammed Danishb, , M.N. Mohamad Ibrahimc, Rokiah Hashimd a Faculty of Pharmacy and Health, Universiti Kuala Lumpur, Royal College of Medicine, Ipoh Perak, Malaysia, 30450 b Green Chemistry and Sustainable Engineering Technology Research Cluster, Universiti Kuala Lumpur Malaysian Institute of Chemical and Bioengineering Technology (MICET), Lot 1988, Kawasan Perindustrian Bandar Vendor, Taboh Naning, 78000 Alor Gajah, Melaka, Malaysia c School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia d Division of Bioresource, Paper and Coatings Technology, School of Industrial Technology, Universiti Sains Malaysia, 11800 Penang, Malaysia
    Keywords:
    Silver nanoparticles
    Bovine serum albumin
    Anticancer effect
    Apoptotic activity 
    The aim of the current study was to biosynthesize the silver nanoparticles (AgNPs) from the bacterial strain of Bacillus cereus (ATCC 14579) extracellularly. When bacterial extract was challenged with 1 mM silver nitrate (AgNO3) the color of the extract changed into brown confirms the formation of nanoparticles. These nano-particles were capped with bovine serum albumin (BSA). UV- visible spectroscopy showed the absorption peak at 420 nm indicates the formation of AgNPs. Fourier Infra –red (FTIR) attenuated total reflection (ATR) spectro-scopy showed amide and amine group associated with AgNPs that stabilizes the nanoparticles. Energy dispersive x-ray spectroscopy (EDX) showed a strong peak of silver confirms the presence of silver. Thermo gravimetric analysis (TGA) analysis was used to determine the protein degradation showed less protein degradation at higher temperature confirms the stability of nanoparticles. Transmission electron microscopy (TEM) showed the AgNPs are well dispersed and spherical, and 5.37 nm to 17.19 whereas albumin coated nanoparticles are size ranges from 11.26 nm to 23.85 nm. The anticancer effect of capped AgNPs (cAgNPs) showed the IC50 value against breast cancer MCF-7 at 80 μg/mL, intestinal colon cancer HCT- 116 60 μg/mL, and bone cancer osteosarcoma MG-63 cell line80 μg/mL while against normal fibroblast cells 3T3 cells showed the IC50 value at 140 μg/mL. Lactate dehydrogenase assay (LDH) showed higher toxicity on MCF-7, HCT-116, and MG-63 cells. The apoptotic study clearly showed the blebbing of membrane, chromatin condensation due to the production of reactive oxygen species (ROS) by ethidium bromide and acridine orange dual staining method. The DNA analysis showed the complete fragmentation of the DNA of treated cells when compared with control cells.