Abstract
Antiproliferative and apoptotic effects of ethyl acetate from the root of Polygonum cuspidatum (EAPC) and its bioactive compound, emodin, in colorectal adenocarcinoma HT-29 cells were investigated. HPLC analysis of major compounds, cell viability by MTT assay, the Comet assay, determination of reactive oxygen species (ROS) levels, apoptosis assay by flow cytometry and Western blot analysis were conducted. The results show significant antiproliferative effects of EAPC, IC50 = 141.4 μg/mL, and emodin isolated from EAPC, IC50 = 73.0 μg/mL, on HT-29 cells. HT-29 cells which were exposed to EAPC and emodin exerted apoptosis, after annexin V FITC/PI staining. EAPC (at 200 μg/mL) and emodin (at 100 μg/mL) increase DNA damage in HT-29 cells by 75.6% and 67.8%, respectively, supporting that apoptosis occurred when the cells were treated with EAPC and emodin. Cells treated with EAPC and emodin generated intracellular ROS. In addition, emodin at tested doses of 25-100 μg/mL suppressed nuclear factor κB (NFκB) and enhanced activator protein 1 (AP-1), which are involved in both proliferation and apoptosis events. EAPC and emodin demonstrated significant anti-proliferation of HT-29 cells through their pro-oxidant activity and contribution to oxidative stress, which in turn leads to cell death. EPAC and emodin inhibited HT-29 cell growth via apoptosis and could be considered as potential candidates for anti-colorectal cancer treatment.
Highlights
Several epidemiological studies have provided convincing evidence that a large body of cancer-related deaths is closely linked to unhealthy diet and lifestyle
high performance liquid chromatography (HPLC) Chromatograms and UV Spectra of EAPC and Emodin Figure 1 shows that the identification of the bioactive compounds of EAPC was conducted by HPLC as compared to page no: 19
Treatment of HT-29 cells with 100 μg/mL of emodin for 24 h induced on increment of 67.8% with respect to the control
Summary
Several epidemiological studies have provided convincing evidence that a large body of cancer-related deaths is closely linked to unhealthy diet and lifestyle. Different cancer treatments have produced different side effects, including nausea, pain and fatigue, which can make patients uncomfortable and affect their ability to stick to their treatments[2]. Current treatment of colorectal cancer generally employs surgical resection combined with chemotherapy and radiation therapy[3]. This treatment is not fully successful for late stage colorectal cancer patients[3]. A number of studies have shown that high consumption of vegetables, fruits, photochemical and chemo preventive agents from natural products decreases the risk of colorectal cancer. Development of novel agents from plant-derived natural products can potentially provide a beneficial and valuable source for anti-colorectal cancer treatment
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