Abstract Background Shikonin derivatives have cytotoxic and antitumor effects. This study aims to investigate the antitumor effects of acetylshikonin isolated from a Chinese medicinal herb Arnebia euchroma (Royle) Johnst.
Methods The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of acetylshikonin on human lung adenocarcinoma cell line A549, human hepatocellular carcinoma cell line Bel-7402, human breast adenocarcinoma cell line MCF-7 and mouse Lewis lung carcinoma (LLC) cell line. C57BL/6 mice with LLC model were used to study the in vivo antitumor effects of acetylshikonin. The expression of bax, bcl-2 and caspase-3 proteins in LLC tissue was determined with immunohistochemical staining.
Results In A549, Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. IC50 (means ± SD) were 5.6 ± 0.86 μg/ml, 6.82 ± 1.5 μg/ml, 3.04 ± 0.44 μg/ml and 2.72 ± 0.38 μg/ml respectively. Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition rate of acetylshikonin (2 mg/kg) was 42.85%. Immunohistochemical staining revealed that in the acetylshikonin groups the expression of bax and caspase-3 increased, whereas the expression of bcl-2 decreased, suggesting that acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3.
Discussion Recent studies showed that shikonin derivatives acted on multiple tumor cells and triggered multiple cell death pathways. Therefore, shikonin derivatives are potentialcancer treatment agents. Acetylshikonin is a main shikonin derivative of Arnebia euchroma (Royle) Johnst. Other research on shikonin derivatives also demonstratedthat acetylshikonin inhibited K562 and HL-60 tumor growth ; however, acetylshikonin had not been studied in detail. The present study indicated that acetylshikoninhad in vitro and in vivo antitumor effects. Acetylshikonin possessed a high level of cytotoxic activity in vitro.
Conclusion Acetylshikonin isolated from Arnebia euchroma (Royle) Johnst cell suspension cultures exhibits specific in vivo and in vitro antitumor effects.