Abstract
Background: Cisplatin is an important chemotherapeutic agent that is widely used in treatment of several malignancies, but its side effects on normal tissues and organs limit its use. The aim of this study was to evaluate the effect of aqueous extract of sweet fennel alone and in combination with cisplatin on human cervical cancer adenocarcinoma cell line (HeLa cells) searching for an effective, inexpensive therapy with minimal side effects. Materials and Methods: HeLa cell line was used to study the cytotoxic effect of different concentrations of the aqueous extract of sweet fennel alone and in combination with 50 mu g/ml cisplatin. Quantitative measure of drug interaction was quantified by the combination index. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used to analyze the sweet fennel decoction. MTT assay was used to examine cell viability percentage. Electron microscopy was applied to study the ultrastructure of the cells. Results: The phenyl propanoids (23%) and phenols (12%) constituted the highest percentage of the aqueous extract. Increasing the concentration of sweet fennel from 50 mu g/ml to 80 mu g/ml, decreased the percentage of the cell viability of HeLa cells from 86.74% to 78.28%, respectively. Further decrease to 11.31% was demonstrated when 50 mu g/ml of fennel was combined with 50 mu g/ml cisplatin (additive effect). In addition to the signs of apoptosis observed in HeLa cells at 50 mu g/ml of fennel, disruption of both nuclear and cytoplasmic membranes and presence of autophagolysosomes were noticed at a dose of 80 mu g/ml. Combination of 50 mu g/ml of cisplatin with 60, 70, and 80 mu g/ml of sweet fennel revealed no significant difference in comparison to cisplatin alone. The combination with 50 mu g/ml of sweet fennel revealed marked vacuolization of the cytoplasm, fragmentation of the nucleus, and complete disruption of nuclear membrane. Conclusion: Combination of cisplatin and the 50 mu g/ml of the fennel could enhance cervical cancer growth inhibition. This combination could be effective in lowering the dose of single or repeated cumulative courses of cisplatin and hence decreases its hazardous side effects. In vivo studies and the evaluation of different combination doses of cisplatin and sweet fennel are recommended.