Cellular And Molecular Impacts Of Titania Nanotube Arrays Interaction With Human Colorectal Cancer Cell Lines HT-29. Human Osteosarcoma Cell Lines SAOS-2 And Human Dermal Fibroblast Cell Lines HDF-A

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Date
2016-09
Authors
S.M.N. Mydin, Rabiatul Basria
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Abstract
The unique structure of Titania Nanotube Arrays (TNA) provides larger surface area and energy to improve cellular interactions for nano-biomaterial implants and nanomedicine applications. However, the nano-complexity properties of TNA have also contributed to the daunting task in ensuring the safety and nano-genotoxicity risk. The present cell-TNA study has provided profound understanding in the effect on genes and proteins that involved in regulation of cellular survival and cell growth signals (p53, AKT1, SKP2, P27, RB and BCL2), activation of DNA damage and DNA repair mechanisms (XRRC5, RAD50) and activation of redox regulator pathways targeted for an antioxidant defence in order to protect DNA from oxidative challenge during cellular division (GADD45, MYC, CHEK1 and ATR). Additionally, flow-cytometry analysis revealed the cell-TNA interaction could caused cell cycle arrest at G0/G1 phase indicating that this stimulus might be involved in DNA damage surveillance mechanisms. Furthermore, the cell fate decision of cell-TNA interaction (adaptive capacity to an environment) might possibly be involved in the cellular senescence via NF-κB pathway. It has been revealed in this study that cell-TNA interaction triggers the telomere shortening activity and inhibition of telomerase activity at mRNA and protein level. The present work supported that cell-TNA stimulus might involve controlled transcription and proliferative activities via NBN and TERF21P mechanisms. Moreover, inhibition of NF-κB may promote molecular sensitivity via cellular senescence by senescence-associated secretory phenotype (SASP) activities and might results in reduced inflammatory response, which would be good for future osseointegration feedback. In addition, the cell-TNA nano-mechanical-adaptation response could also activate genes regulation at mRNA and protein level that are involved in cytoskeleton remodelling of extracellular matrix alterations for tensile and shear stiffness response (KEAP1, AREG, B2M, CTGF, TRFC, KRT8 and COL7A1) along with the plasma membrane modulations and intracellular signalling response for the cell polarity and adhesion (NQO1, ABL1, UBC, KRAS, AKT1, OGFR, CAV1 and GJA1) in addition to the locomotory behaviour and cell metabolism mechanisms for the mechanosensitivity activities (GAPDH, PGK1, MDK, FIGF, HPRT and DES). Based on these findings, the intricate molecular mechanism behind cell-TNA interactions are crucial for positive cell growth regulation and nanosurface mechanosensitivity activities which could contribute for better cellular responses. As for advanced medical application, this nanomaterialmolecular knowledge are beneficial for further nanomaterial characterisation.
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Titania nanotube arrays interaction , with human colorectal cancer cell line
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