Gallic acid and methyl gallate enhance antiproliferative effect of cisplatin on cervical cancer (HeLa) cells

Cervical cancer is the fourth most common cancer-related death affecting women. The drug resistance, toxicities and undesired side effects become the major limitation in cisplatin-based chemotherapy. Gallic acid and methyl gallate are the most abundance phenolic compounds that are widely distributed in plants. This study was conducted to evaluate the antioxidant and antiproliferative activity of gallic acid and methyl gallate and their synergistic effects in combination with cisplatin towards cervical cancer (HeLa) cells. The antioxidant activity of gallic acid and methyl gallate was measured by using 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Antiproliferative activity of gallic acid, methyl gallate and cisplatin on HeLa and NIH/ 3T3 cells was determined using MTT assay. The effect of gallic acid and methyl gallate combined with cisplatin were then determined by CompuSyn software. Gallic acid and methyl gallate showed strong antioxidant activity with EC50 value of 18.23 µM and 19.39 µM, respectively. The IC50 of gallic acid, methyl gallate and cisplatin on HeLa cells were 13.44 µg/mL, 16.55 µg/mL, and 8.04 µg/mL whereas in NIH/3T3 cells were 32.90 µg/mL, 35.70 µg/mL, and 6.57 µg/mL. Cisplatin combined with fixed concentration of gallic acid and methyl gallate could inhibit the proliferation of HeLa cells greater than cisplatin alone. Interestingly, gallic acid and methyl gallate in combination with cisplatin at the concentration of 0.51-4.02 µg/mL have shown synergistic effects. Therefore, our study suggested that gallic acid and methyl gallate in combination with cisplatin have the potential to be developed as chemotherapeutic agents for cervical cancer

Combination effect of tamoxifen and ascorbic acid treatment on breast cancer cells (MCF-7) and cervical cancer cells (HeLa)

Breast cancer and cervical cancer are among the leading causes of death among women in the world. Even though chemotherapy is available as cancer treatment, the development of drug resistance in both cancer cells has reduced the efficacy of chemotherapeutic drugs in such treatment. The current study was aimed to evaluate the cell viability of human breast cancer cells, MCF-7, and cervical cancer cells, HeLa upon the combination treatment of ascorbic acid and tamoxifen. The cell viability was measured using the MTT assay, with an incubation period of 72 hours in a humidified CO2 incubator. The concentrations of tamoxifen and ascorbic acid that reduced 50% of the cell population (IC50) were determined from the dose-response curve. The IC50 concentration was used to determine the cell viability in the treated cells. CompuSyn software was used to evaluate the combined effects towards both cells upon treatment and the results were calculated as combination index (CI). The data were analyzed using GraphPad Prism (version 7). Statistical analysis was performed using an independent t-test. The IC50 values of tamoxifen and ascorbic acid on MCF-7 cells were 14.53 μg/ml and 15.8 μg/ml respectively, while the IC50 values of tamoxifen and ascorbic acid on HeLa cells were 11.09 μg/ml and 202.3 μg/ml respectively. The combination of tamoxifen and ascorbic acid exerted a greater growth reduction percentage in both cells compared to tamoxifen alone. The results indicated that ascorbic acid synergizes the cytotoxic effect of tamoxifen at lower concentrations towards MCF-7 cells with a CI less than 1. However, the combination of tamoxifen and ascorbic acid exerted an antagonistic effect in HeLa cells, with a CI more than 1

Xanthine oxidase inhibitory and DPPH radical scavenging activities of some primulaceae species

Xanthine oxidase (XO) is an enzyme that catalyzes the metabolism of hypoxanthine and xanthine into uric acid. XO also serves as an important biological source of free radicals that contribute to oxidative damage involved in many pathological processes. Antioxidant effects of several Primulaceae species have been reported but their XO inhibitory activity has not been investigated. Thus, this study was conducted to determine the XO inhibitory and free radical scavenging activities of Primulaceae species and to correlate these activities with their total phenolic contents (TPC). A total of 129 extracts of different plant parts of twelve Primulaceae species were assayed for XO inhibition spectrophotometrically at 290 nm using allopurinol as a positive control. The antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and TPC of the extracts were determined by the Folin-Ciocalteau method. The Pearson correlation analysis indicated that the TPC of the extracts showed moderate positive correlations with XO inhibition (r=0.31, p<0.05) and DPPH antioxidant activity (r=0.31, p<0.05) for all of the dichloromethane extracts. Amongst the extracts tested, the dichloromethane extract of the roots of Labisia pumila var. alata showed the strongest inhibitory effects for XO (IC50 4.8 μg/mL) and DPPH free radical capacity (IC50 1.7 μg/mL). The results suggested that Primulaceae species, particularly the dichloromethane extract of L. pumila var. alata roots, are the potential source of useful leads for the development of XO inhibitors