Anti-tumor Effects Of Alkaloids From TCM Sophora Plants

In recent thirty years, the quinolizidine alkaloids isolated from Traditional Chinese Medicine(TCM) genus Sophora have received more attention. The genus Sophora commonly used asTCM herbs include Sophora Flavescens Ait, Radix Sophorae Tonkinensis and SophoraAlopecuroide L. All of them contain quinolizidine alkaloids such as matrine-type (matrine,sophoridine, sophocarpine and oxymatrine), aloperine-type, sparteine-type and cytisine-type.Sophora Flavescens or Radix Sophorae Tonkinensis has been used as a component in variousTCM formulations to treat tumor patients. Likewise, matrine or sophoridine has been usedclinically as a cancer therapeutic agent in China. Here we investigated the in vitro anti-tumoractivities of seven quinolizidine alkaloids against several malignancies with higher incidence inChina, including lung cancer, digestive system cancer and leukemia.Firstly, we examined the purities of matrine, sophoridine, sophocarpine, oxymatrine,aloperine and cytisine using High-performance liquid chromatography (HPLC). The resultsshowed that the alkaloids have the purities higher than 96 % with the exception of sparteinewhich has a purity greater than 99 %. Using MTT assay, we measured the growth-inhibitioneffects of the seven quinolizidine alkaloids on human lung cancer cell line A549, humanhepatoma cell line HegG2, human esophageal carcinoma cell line EC109 and human leukemiaK562, HL-60, U937 cells. The results showed that among the alkaloids, aloperine exerted thestrongest growth-inhibition effect against the tested tumor cells and the most evident inhibitionwas observed in leukemia cell line HL-60. Using DNA fragmentation assay, DNA ladder wasobserved after leukemia cell line HL-60 exposed to 0.02mM aloperine for 48h. Usingwestern-blot assay, cleavage of PARP was found to be in a dose- and time- dependent manner.The results suggested that aloperine induced apoptosis in leukemia cell line HL-60.Using Acridine orange (AO) assay, autophagy was analyzed in leukemia cell line HL-60exposed to 0.05 mM aloperine for 18h. Aloperine treatment resulted in a dose-dependentincrease of autophagic cells. In conclusion, the seven quinolizidine alkaloids derived from Sophora Plants havegrowth-inhibition actions against the six tumor cell lines. Among the alkaloids, aloperine exertedthe most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrineexhibited selective anti-cancer activity against hepatocellular carcinoma cell line HepG2.