| Summary: | Combination of chemotherapeutic agent and chemopreventive agent is
being a new approach in cancer treatment. This is aimed at enhancing the
effectivity and also reducing drug resistance and adverse side effect of the
chemotherapeutic agent. Hesperidin, a citrus flavonoid has been reported to
reduce the proliferation of many cancer cells. The objectives of this study were to
investigate cytotoxic activities, cell cycle modulation and apoptosis induction of
hesperidin and its combination with doxorubicin on Hela cell lines. MTT [3-(4,5-
dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide] assay was used to
measure the growth inhibitory effect of hesperidin and its combination with
doxorubicin on Hela cells. Cell cycle profile was determined by flowcytometry
and the data obtained was analyzed by using ModFit LT 3.0 program. Apoptosis
assay was done using double staining method using ethidium-bromide and
acridine-orange.
Hesperidin inhibited cell growth with IC50 48 μM, while the IC50 of
doxorubicin was 1 μM. Combination of 5 μM doxorubicin and 6 μM hesperidin
showed strongest inhibitory effect toward Hela cells which save 3,28% of cell
viability. Hesperidin of 24 µM accumulated HeLa cells at G1 phase, while
doxorubicin of 5 μM accumulated HeLa cells at S phase. Combination of 24 μM
hesperidin with 5 μM doxorubicin gave G1 and S phase accumulation at 24 h
incubation. All of Hesperidin and Doxorubicin were capable of inducing
apoptosis. Their combination increased apoptosis of HeLa sel compared with
single treatment. In accordance of this apoptosis induction effect,
imunocytochemistry method was conduct to determine the level of Bcl-2 and Bax
expression. It is showed that hesperidin, doxorubicin and their combination
decreases the expression Bcl-2 and increases the expression of Bax. According to
this results, hesperidin has a potency to be developed as co-chemotherapeutic
agent for cervical cancer.
|
|---|