Objective

The fatality of cancer is mostly dependent on the possibility of occurrence of metastasis. Thus, if the development of metastasis can be prevented through novel therapeutic strategies targeted against this process, then the success of cancer treatment will drastically increase. In this study, therefore, we evaluated the antimetastatic potentials of an extract of Khaya senegalensis and curcumin on the metastatic liver cell line HepG2, and also assessed the anticancer property of the extract.

Methods

Cells were cultured and treated with graded concentrations of test substances for 24, 48, or 72 h with provisions made for negative controls. Treated cells were assessed as follows: nanotechnologically - atomic force microscopy (AFM) was used to determine cell stiffness; biochemically - cell cytotoxicity, glutathione level and adenosine triphosphate status, caspase activation and mitochondrial toxicity were considered; and microbiologically - a carrot disk assay was used to assess the anticancer property of the extract of K. senegalensis.

Results

Curcumin and K. senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively, indicating their antimetastatic effects. Corresponding changes in redox (glutathione level) and energy (adenosine triphosphate) status of the cells were also demonstrated. Further mechanistic studies indicated that curcumin was not mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the extract potently inhibited the Agrobacterium tumefaciens-induced genetic transformation based on carrot disk assay.

Conclusion

Cell elasticity measurement data, using AFM, strongly suggested, for the first time, that both curcumin and the extract of K. senegalensis exhibited antimetastatic properties on HepG2 cells.

Background

Epidemiological and experimental evidences have shown cancer as a leading cause of death worldwide. Although the folklore use of plants as a reliable source of health-restoring principles is well-documented, the search for more of such plants that are active against diseases, such as cancer, continues. We report here a laboratory-based evidence of the relevance of an ethanol leaf extract of Anogeissus leiocarpus (A2L) in comparison with resveratrol, a natural polyphenol, in cancer therapy.

Methods

The quantitative assessment of flavonoid and phenolic contents involved quercetin and gallic acid as standards, respectively were determined using spectrophotometry. Cytotoxicity was determined fluorometrically using propidium-iodide-staining method. Antioxidant status, adenosine triphosphate (ATP) levels, caspase activities and mitochondrial integrity were assessed using fluorometry/luminometry.

Results

The antioxidant assay demonstrated that A2L possesses a strong antioxidant capacity as compared with the reference compounds, ascorbic acid and butylated hydroxytoluene. This is further buttressed by the significantly high level of phenolics obtained in the quantitative assessment of the extract. A 72-h post-treatment examination indicated that both A2L and resveratrol modulate the proliferation of HepG2 liver carcinoma cells in a time- and concentration-dependent manner. Determination of the total nuclei area, propidium-iodide negative and positive nuclei areas all further buttress the modulation of cell proliferation by A2L and resveratrol with the indication that the observed cell death is due to apoptosis and necrosis at lower and higher concentrations of treatments respectively. At lower concentrations (0.39-3.13 μg/mL), resveratrol possesses higher tendencies to activate caspases 3 and 7. Bioenergetically, both resveratrol and A2L do not adversely affect the cells at lower concentrations (0.39-6.25 μg/mL for resveratrol and 12.5-100.0 μg/mL for A2L) except at higher concentrations (12.5-25.0 μg/mL for resveratrol and 200-800 μg/mL for A2L) which are more pronounced in A2L-treated cells. Furthermore, the antioxidant status of HepG2 cells is not perturbed by resveratrol as compared with A2L. Assessment of 24-h post-treatment mitochondrial function shows that resveratrol is not mitotoxic as compared with A2L which exhibits mitotoxicity at its highest concentration.

Conclusions

Taken together, findings from this study showed that A2L possesses strong antiproliferative activity and its prospect in the management of hepatocellular carcinoma deserves further investigation.