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Screening of a Small Flavonoid Library for Anti‐Cancer Activity Against Glioblastoma
Author(s) -
Faler Ashton D.,
Stang Christopher R.T.,
Khupse Rahul S.,
Schneider Ryan A.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.823.4
Subject(s) - chemistry , chalcone , u87 , flavonoid , cell culture , glioblastoma , apoptosis , cytotoxic t cell , cancer cell , cytotoxicity , pharmacology , mtt assay , antioxidant , cancer , biochemistry , traditional medicine , in vitro , cancer research , stereochemistry , biology , medicine , genetics
Flavonoids, including chalcones and flavanones, have been highly studied for their multitude of activities including antioxidant and anti‐cancer effects. We previously demonstrated that several of our chalcone derivatives had IC 50 values in the low micromolar range in multiple distinct human cancer cell lines, but appeared to be most potent against A‐172 glioblastoma cells. The poor prognosis of glioblastoma necessitates further investigations to identify more effective treatment options. To determine if the activity of these chalcones was comparable in additional glioblastoma lines, our small library of flavonoids was screened against T98G and U87 MG glioblastoma cells. Our library consisted of eight flavonoid derivatives; six of which were chalcones and two flavanones. IC 50 values, as measured by the CyQuant NF or XTT cell proliferation assay, were noted to be in the low micromolar range for three of these compounds; RK6, RK7, and RK15. RK6 had an IC 50 of 9 μM and 20 μM against the T98G and U87 MG cell lines respectively. RK7 displayed IC 50 values of 33 μM and 51 μM against the T98G and U87 MG cell lines respectively. RK15 was the most potent chalcone derivative with IC 50 values of 3 μM in T98G cells and 5 μM in U87 MG cells. A Caspase‐Glo 3/7 assay was utilized to investigate the mechanism by which these compounds exhibited their cytotoxic effects. A significant increase in effector caspase activity was noted following treatments with RK6, RK7, and RK15 in both T98G and U87 MG cells. Furthermore, partial reversal of apoptosis by the pan‐caspase inhibitor, Z‐VAD‐FMK, suggests that caspases are involved in the observed cell death by RK6, RK7, and RK15 in these glioblastoma cell lines. Further investigations are ongoing with these chalcones to determine the molecular mechanisms of cell death in glioblastoma cells and to optimize the structure activity relationship. Support or Funding Information This work was supported in part by an Individual Summer Undergraduate Research Fellowship sponsored by ASPET for the first author.