Abstract
Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumors RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.
Highlights
traditional Chinese medicine (TCM) Realgar is the ore of sulfide mineral Realgar, which consists of a series of arsenic-containing metal sulfides (AS4S4) (Xuemin, 2000; National Pharmacopoeia Committee 2004)
The results indicated that Realgar Bioleaching Solution (RBS) extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner
Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner
Summary
TCMs Realgar ( named “Xiong-Huang” in Chinese) is the ore of sulfide mineral Realgar, which consists of a series of arsenic-containing metal sulfides (AS4S4) (Xuemin, 2000; National Pharmacopoeia Committee 2004). According to ancient medical records and recent findings in clinical trials, realgar was found as effective as arsenic trioxide (ATO), but with relatively good oral safety profiles even on chronic administration. These give realgar an advantage over ATO in maintenance treatment. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. On RBS administration to mice, arsenic was targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment
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