Implications of enhanced effectiveness of vincristine sulfate/ε - viniferin combination compared to vincristine sulfate only on HepG2 cells

Yıl 2016, Cilt: 43 Sayı: 4, 534 - 541, 25.12.2016

Filiz Özdemir , Zerrin İncesu Mesut Şena Nur İpek Öndera Miris Dikme

Öz

Objective: This study was designed to investigate the
effects of ε-viniferin (ε-VNF) on the mitochondrial pathway of apoptosis
and on late apoptosis in HepG2 cell lines. To observe these effects,
ε-VNF and vincristine sulfate (VNC), anti-cancer drugs used for
treatment on HepG2 cells, were administered either alone or in
combination at different time intervals.

Methods: Mitochondrial membrane potential changes in
the cells (ΔΨm) were evaluated using cationic dye JC-1, while Bax, Bcl-2
expression levels with RT-PCR and caspase-3 activity were analyzed
using a kit. For detection of apoptotic activity, an in situ TUNEL assay
was performed.

Results: When 98.3µM ε-VNF, 52.5µM VNC and the
11.25+15.8µM VNC+ε-VNF combination were compared with the control group,
ΔΨm changes at the 6th hour were found to be 19.5%, 5.5%, 24.6%, and
3.5% , respectively. These finding show that the combination group
(24.6%) resulted in early apoptosis of the cell at the 6th hour. Bax
mRNA expression increased at the 24th hour in the VNC+ε-VNF group
compared to control group (160%), and caspase-3 activation increased in
the 1.25+15.8 µM[VNC+ε-VNF] group compared to the control group at the
48th hour. The detection of DNA fragments in HepG2 cells within 24 hours
suggests direct apoptosis.

Conclusion: These findings demonstrate that the doses
administered to the VNC+ε-VNF combination group were lower than those
administered to groups using one agent alone (e.g. VNC), the results of
which reduce the possibility of administering toxic doses.

Anahtar Kelimeler

viniferin, vincristine, HepG2 cell

Kaynakça

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