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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Keywords
Titania nanotube arrays interaction , with human colorectal cancer cell line