Abstract
Background: Rumex dentatus, commonly known as tooth docked, is widely used in traditional system of medicines. Although it is well reported for its biological activities and medicinal value, only few studies have been carried out to assess its anticancer potential.Purpose: This study seeks to evaluate the anticancer activity of leaf extracts of R. dentatus against breast cancer MDA-MB-231 cell line, a triple negative human breast cancer cell line with invasive properties and to identify the molecular targets underlying its mechanism of action.Methods: Cytotoxicity of plant extracts was determined against breast cancer cells, using the MTT assay. Flow cytometry was performed to analyze the changes in cell cycle and apoptotic effect, if any. Cells were also studied for their wound healing and invasive potential as well as for Western blotting of apoptotic genes and nuclear factor-kappaB (NF-κB) pathway.Results: The results revealed that R. dentatus methanol (RM) and chloroform (RC) extracts of R. dentatus had the highest inhibition of cell proliferation in a concentration- and time-dependent manner. This inhibitory effect was found to be linked to arrest of cell cycle at the G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. Moreover, it was shown that both RM and RC inhibited the proliferation of the malignant cells and induced apoptosis by repressing the activation of NF-κB and its subsequent transcripts, Bcl-xl, Bcl-2, Cyclin D1, survivin, and XIAP. Apoptosis was also confirmed in the cells as suggested by caspase-3 detection. RM and RC also abrogated IκBa phosphorylation in the malignant cells as well as reduced the invasive and migratory capabilities of these cells.Conclusion: Our findings suggest that the methanol and chloroform extracts of R. dentatus may have anti-cancer compounds that are potentially useful in the treatment of human breast cancer.
Highlights
Despite significant progress in modern cancer research, breast cancer remains the most common malignancy and the major causative agent of death in women, especially in developed countries (Farshori et al, 2013)
Our results revealed that all the extracts suppressed the proliferation of MDA-MB-231 breast cancer cell line in a time- and concentration-dependent manner, except Rumex dentatus n-hexane (RH), which caused increase in cell death rate, but only with increase in time
According to the MTT assay results based on IC50 values, the lowest concentration of extracts that was responsible for 50% loss of cell viability in MDA-MB-231 cell line was about 116 μg/ml for the non-polar Rumex dentatus chloroform (RC) extract, followed by R. dentatus methanol (RM) extract with IC50 of 139 μg/ml after 24 h treatment (Figure 1A)
Summary
Despite significant progress in modern cancer research, breast cancer remains the most common malignancy and the major causative agent of death in women, especially in developed countries (Farshori et al, 2013). The anthracycline, doxorubicin (DOX), which has high efficacy as an antibreast cancer agent is associated with cardiotoxicity, including development of a cardiomyopathy (Weiss, 1992). This limits the chemotherapeutic use of DOX (Lefrak et al, 1973). Commonly known as tooth docked, is widely used in traditional system of medicines. It is well reported for its biological activities and medicinal value, only few studies have been carried out to assess its anticancer potential. Purpose: This study seeks to evaluate the anticancer activity of leaf extracts of R. dentatus against breast cancer MDA-MB-231 cell line, a triple negative human breast cancer cell line with invasive properties and to identify the molecular targets underlying its mechanism of action
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