Abstract
This study was to investigate the synergistic effect of NB/Cur on growth and apoptosis in A375 human melanoma cell line by MTT assay, flow cytometry and Western blotting. Our results demonstrated that NB effectively synergized with Cur to enhance its antiproliferative activity on A375 human melanoma cells by induction of apoptosis, as evidenced by an increase in sub-G1 cell population, DNA fragmentation, PARP cleavage and caspase activation. Further mechanistic studies by Western blotting showed that after treatment of the cells with NB/Cur, up-regulation of the expression level of phosphorylated JNK and down-regulation of the expression level of phosphorylated ERK and Akt contributed to A375 cells apoptosis. Moreover, NB also potentiated Cur to trigger intracellular ROS overproduction and the DNA damage with up-regulation of the expression level of phosphorylated ATM, phosphorylated Brca1 and phosphorylated p53. The results indicate the combinational application potential of NB and Cur in treatments of cancers.
Highlights
Curcumin (Cur), bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione, shown in Figure. 1A, is an active ingredient from the rhizome of the plant, Curcuma longa, which is widely used in food industry as a spice, coloring agent, food preservative and in traditional medicine as an ingredient [1,2,3]
At concentration of 40 mg/ml, natural borneol (NB) reduced the cell viability of 10 mM Cur-treated cells from 70% to 54.20%. These results indicated that pretreatment of the cells with NB (40 mg/ml) caused significantly stronger cell growth inhibition than Cur alone, as evidenced by a decrease in IC50 of Cur from 16.4 to 9.5 mM
Pretreatment of the cells with 40 mg/ml NB for 12 h followed by simultaneous incubation with 10 mM Cur for 72 h resulted in much stronger growth inhibition by comparing with Cur and NB alone
Summary
Curcumin (Cur), bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione, shown in Figure. 1A, is an active ingredient from the rhizome of the plant, Curcuma longa, which is widely used in food industry as a spice, coloring agent, food preservative and in traditional medicine as an ingredient [1,2,3]. Many studies demonstrated that Cur possessed wide-ranging antioxidant, anti-inflammatory, antiproliferative, anti-angiogenic and anti-cancer activities [4,5]. Numerous studies reported the anticancer effect of Cur on a wide variety of cancer cell lines, including hepatocellular carcinoma cell lines [6], thyroid cancer cells [3], colon cancer cells [7,8,9], breast cancer cells [10], bladder cancer cells [11], ovarian cancer cells [5,12] and so on. Combination of Cur and other drugs was reported to improve the bioavailability of Cur due to increasing the cellular uptake of Cur [15]. Enhancement of the cellular uptake of Cur could be a strategy to improve its anti-cancer activities
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