title: Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells.
abstract: Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells.
authors.affiliation: College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China. zhangxf9465@163.com.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China. yanyy75@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China. shenwei427@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul 143-701, Korea. gsangiliyandi@yahoo.com.
authors.forename: Sangiliyandi
authors.initials: S
authors.lastname: Gurunathan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
chemical_list: D006877:Hydroxamic Acids; C012589:trichostatin A; D010165:Palladium; D053148:Caspase 3; D006655:Histone Deacetylases
keywords: apoptosis; caspases; cell viability; cervical cancer; mitochondrial membrane potential; oxidative stress; palladium nanoparticles; trichostatin A