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AuthorAlhoshani A.
AuthorAlrashdi A.
AuthorAlhosaini K.
AuthorAlanazi F.E.
AuthorAlajez N.M.
AuthorAltaf M.
AuthorIsab A.A.
AuthorKorashy H.M.
Available date2020-02-24T08:57:13Z
Publication Date2018
Publication NameSaudi Pharmaceutical Journal
ResourceScopus
ISSN13190164
URIhttp://dx.doi.org/10.1016/j.jsps.2018.05.012
URIhttp://hdl.handle.net/10576/12991
AbstractGold complex bis(diethyldithiocarbamato-gold(I)) bis(diphenylphosphino) methane (BDG-I) is cytotoxic toward different cancer cell lines. We compared the cytotoxic effect of BDG-I with that of cisplatin in the A549 lung cancer cell line. Additionally, we investigated the molecular mechanism underlying the toxic effect of BDG-I toward the A549 cell line and the identification of cancer-related miRNAs likely to be involved in killing the lung cancer cells. Further, X-ray crystallographic data of the compound were acquired. Using microarray, global miRNA expression profiling in BDG-I-treated A549 cells revealed 64 upregulated and 86 downregulated miRNAs, which targeted 4689 and 2498 genes, respectively. Biological network connectivity of the miRNAs was significantly higher for the upregulated miRNAs than for the downregulated miRNAs. Two of the 10 most upregulated miRNAs (hsa-mir-20a-5p and hsa-mir-15b-5p) were associated with lung cancer. AmiGo2 server and Panther pathway analyses indicated significant enrichment in transcription regulation of miRNA target genes that promote intrinsic kinase-mediated signaling, TGF-?, and GnRH signaling pathways, as well as oxidative stress responses. BDG-I crystal structure X-ray diffraction studies revealed gold?gold intramolecular interaction [Au?Au = 3.1198 (3) �] for a single independent molecule, reported to be responsible for its activity against cancer. Our present study sheds light on the development of novel gold complex with favorable anti-cancer therapeutic functionality.
SponsorThe authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through the Research Project No. R5-16-02-14 .
Languageen
PublisherElsevier B.V.
SubjectChrysotherapeutic agents
Gold
Lung cancer
miRNA
TitleGold-containing compound BDG-I inhibits the growth of A549 lung cancer cells through the deregulation of miRNA expression
TypeArticle
Pagination1035 - 1043
Issue Number7
Volume Number26
dc.accessType Open Access


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