title: Enhancement of Cytotoxicity and Inhibition of Angiogenesis in Oral Cancer Stem Cells by a Hybrid Nanoparticle of Bioactive Quinacrine and Silver: Implication of Base Excision Repair Cascade.
abstract: A poly(lactic-co-glycolic acid) (PLGA)-based uniform (50-100 nm) hybrid nanoparticle (QAgNP) with positive zeta potential (0.52 ± 0.09 mV) was prepared by single emulsion solvent evaporation method with bioactive small molecule quinacrine (QC) in organic phase and silver (Ag) in aqueous phase. Physiochemical properties established it as a true hybrid nanoparticle and not a mixture of QC and Ag. Antitumor activity of QAgNP was evaluated by using various cancer cell lines including H-357 oral cancer cells and OSCC-cancer stem cell in an in vitro model system. QAgNP caused more cytotoxicity in cancer cells than normal epithelial cells by increasing BAX/BCL-XL, cleaved product PARP-1, and arresting the cells at S phase along with DNA damage. In addition, QAgNPs offered greater ability to kill the OSCC-CSCs compared to NQC and AgNPs. QAgNP offered anticancer action in OSCC-CSCs by inhibiting the base excision repair (BER) within the cells. Interestingly, alteration of BER components (Fen-1 and DNA polymerases (β, δ, and ε) and unalteration of NHEJ (DNA-PKC) or HR (Rad-51) components was noted in QAgNP treated OSCC-CSC cells. Furthermore, QAgNP significantly reduced angiogenesis in comparison to physical mixture of NQC and AgNP in fertilized eggs. Thus, these hybrid nanoparticles caused apoptosis in OSCC-CSCs by inhibiting the angiogenesis and BER in cells.
authors.affiliation: Cancer Biology Division, KIIT School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.
authors.forename: Shakti Ranjan
authors.initials: SR
authors.lastname: Satapathy
authors.affiliation: Cancer Biology Division, KIIT School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Siddharth
authors.affiliation: Cancer Biology Division, KIIT School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.
authors.forename: Dipon
authors.initials: D
authors.lastname: Das
authors.affiliation: Cancer Biology Division, KIIT School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.
authors.forename: Anmada
authors.initials: A
authors.lastname: Nayak
authors.affiliation: Cancer Biology Division, KIIT School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.
authors.forename: Chanakya Nath
authors.initials: CN
authors.lastname: Kundu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011796:Quinacrine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012834:Silver / Q000008:administration & dosage / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D012834:Silver; D011796:Quinacrine
keywords: hybrid nanoparticle; oral cancer; oral cancer stem cells; quinacrine; silver