TY - JOUR
T1 - Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells
AU - Al-Hrout, Ala’a
AU - Chaiboonchoe, Amphun
AU - Khraiwesh, Basel
AU - Murali, Chandraprabha
AU - Baig, Badriya
AU - El-Awady, Raafat
AU - Tarazi, Hamadeh
AU - Alzahmi, Amnah
AU - Nelson, David R.
AU - Greish, Yaser E.
AU - Ramadan, Wafaa
AU - Salehi-Ashtiani, Kourosh
AU - Amin, Amr
N1 - Funding Information:
This study was supported by AJF grant # 21S098 and UPAR grant # 31S319 for A.A. Authors thanks Ali Alnaqbi at Mechanical Engineering Department, UAEU, for providing HepG2 cells and other logistic support. Y.E.G. was supported by ZCHS grant # 31R049. A.C., B.K., A.A.z., D.R.N. and K.S.-A were supported in part by New York University Abu Dhabi Faculty Research Funds AD060 and by NYUAD Institute grant (G1205-1205i and G1205- 1205g). We thank Marc Arnoux and Mehar Sultana for preparing the RNAseq libraries and carrying out the next generation sequencing at NYUAD sequencing core facility; we thank Nizar Drou and the computational core at NYUAD for the primary and secondary analyses of the RNAseq data.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.
AB - Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.
UR - http://www.scopus.com/inward/record.url?scp=85056700970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056700970&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-34855-0
DO - 10.1038/s41598-018-34855-0
M3 - Article
C2 - 30446676
AN - SCOPUS:85056700970
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 16951
ER -