Abstract
BackgroundLiver cancer is a high incidence and fatal disease, the fifth most frequent cancer worldwide that is usually diagnosed at an advanced stage. The number of deaths from liver cancer has not declined even following various therapies. Plant secondary metabolites and their semi-synthetic derivatives play a principal role in anti-cancer drug therapy, since they are effective in the treatment of specific characteristics while also reducing side effects. Allium atroviolaceum, a plant of the genus Allium has been used in folk medicine to protect against several diseases. However, cytotoxicity and the anti-proliferative effect of Allium atroviolaceum remain unclear. This work aims to investigate the anticancer properties of Allium atroviolaceum and the mechanism of action.MethodsTo evaluate the in vitro cytotoxicity of flower of Allium atroviolaceum, methanol extract at a dose range from 100 to 3.12 μg/ml was assessed against the HepG2 hepatocarcinoma cell line, and also on normal 3T3 cells, by monitoring proliferation using the MTT assay method. A microscopy study was undertaken to observe morphological changes of HepG2 cells after treatment and cell cycle arrest and apoptosis were studied using flow cytometry. The apoptosis mechanism of action was assessed by the level of caspase-3 activity and expression of apoptosis related genes, Bcl-2, Cdk1 and p53. The combination effect of the methanolic extract with doxorubicin was also investigated by determination of a combination index.ResultsThe results demonstrated growth inhibition of cells in both dose- and time-dependent manners, while no cytotoxic effect on normal cell 3T3 was found. The results revealed the occurrence of apoptosis, illustrated by sub-G0 cell cycle arrest, the change in morphological feature and annexin-V and propidium iodide staining, which is correlated with Bcl-2 downregulation and caspase-3 activity, but p53-independent. In addition, a combination of Allium atroviolaceum and doxorubicin led to a significant synergistic effect.ConclusionThese findings suggest that Allium atroviolaceum flower extract has potential as a potent cytotoxic agent against HepG2 cell lines, as it has commendable anti-proliferative activities against human hepatocarcinoma and it can be considered as an effective adjuvant therapeutic agent after the clinical trials.
Highlights
Liver cancer is a high incidence and fatal disease, the fifth most frequent cancer worldwide that is usually diagnosed at an advanced stage
Hepatocellular carcinoma (HCC) is a high incidence and fatal disease that is usually diagnosed at an advanced stage [3], the fifth most frequent cancer worldwide [4] and the third most fatal cancer [5]
Microscopic evaluation of morphological changes in HepG2 cells Morphological changes in the cells and the nuclei were observed under 40X magnification of the inverted phase contrast microscope, aided by acridine orange (AO)/propidium iodide (PI) staining after treatment for 24, 48 and 72 h
Summary
Liver cancer is a high incidence and fatal disease, the fifth most frequent cancer worldwide that is usually diagnosed at an advanced stage. Apoptosis is one of the primary targets for most conventional anti-cancer drugs. Hepatocellular carcinoma (HCC) is a high incidence and fatal disease that is usually diagnosed at an advanced stage [3], the fifth most frequent cancer worldwide [4] and the third most fatal cancer [5]. In 2008, 748,000 liver cancer cases and 696,000 mortalities were estimated worldwide [6]. The inevitable side effects, such as toxicity to normal cells and bone marrow illustrate an instant demand to search for better methods and novel anti-cancer agents that would decrease the mortality rate of HCC with fewer side effects [12]
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