Abstract
High concentrations of arsenic trioxide (As2O3) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As2O3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo. Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As2O3 plus andrographolide. These findings suggest that the combination of andrographolide and As2O3 could yield therapeutic benefits in the treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, causes one million deaths worldwide annually
The results from experiments on Huh7 cells were consistent with those from experiments using HepG2 or SNU449 cells (Supplementary Figure 1A, 1B) These results indicated that andrographolide synergistically enhanced the anti-tumor effects of As2O3 in Hepatocellular Carcinoma
The results showed that the level of EphB4 was decreased under the combination treatment, indicating that EphB4 was affected by the synergy between andrographolide and As2O3 (Figure 3C)
Summary
Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, causes one million deaths worldwide annually. Further research investigating effective therapies for HCC might help prolong the 5-year survival rate. Arsenic trioxide (As2O3) has been used in China for more than 2400 years to treat diverse ailments including tuberculosis and gastric ulcers [5]. As2O3 has been used to treat cancer [6, 7]. Studies have been focused on the effect of As2O3 on solid tumors, including osteosarcoma, gastric carcinoma, colorectal carcinoma, and hepatocellular carcinoma, among others [8,9,10,11]. The high concentrations of As2O3 required to be effective against solid tumors are toxic to normal cells [12]. Andrographolide might act synergistically with As2O3 to increase the latter’s toxic effects on liver cancer cells at reduced As2O3 concentrations
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