Study of the Inhibitory Effects of Chinese Herbal Medicine S10 on the Survival of Glioblastoma and its Stemloids.

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Glioblastoma (GBM) is the most common brain tumor in adults. The current therapy is surgical removal combined with chemical therapy. However, its effect is limited, because of the highly invasiveness and drug resistance of GBM. The studies of Chinese Herbal Medicine (CHM) are scarce compared with those of Western medicines, but CHM has been used in Chinese society for thousands of years. Recently, more studies showed that CHM can effectively inhibit the growth of specific cancer cells. Therefore, we prospect to develop the potential herbs as new treatments for GBM. We used human GBM cell lines, U251-MG and U373-MG, as the drug screening platform to screen herb extracts from Sun Ten Pharmaceutical Company, and identified the herbs which effectively inhibit the growth of GBM cancer cells. The effects of herb extracts on GBM stemloids were further confirmed in U251-derived-tumorspheres and U251-CD133+-tumorspheres. We found that S10 herb extracts effectively inhibits the growth of GBM cancer cell lines, tumorspheres, and CD133+-cancer stem cells. We also showed that S10 does not affect the growth of primary-cultured normal mouse astrocytes. Moreover, we demonstrated that S10 reduces Akt and ERK activation and inhibits the expression of stem cell associated protein, CD133 and Sox2. To confirm the effects of S10 in vivo, we used NOD.CB17-PrKdC-SCID/Jnarl mice injected with CD133+-tumorspheres as xenotransplantation model. S10 extracts inhibits the growth of GBM tumors in mouse. The primary-cultured tumor cells from S10-treated mice showed reduced colony formation ability. Furthermore, we identified one active principle of S10, S10-I2, which also effectively inhibits the growth of GBM cancer cells and GBM stemloids without affect the growth of primary-cultured normal mouse astrocytes. S10-I2 also reduces Akt and ERK activation and inhibits the expression of stem cell associated protein, CD133 and Sox2. In conclusion, S10 and S10-I2 both have significant inhibitory effects on GBM. Moreover, S10-I2 is a potential compound which may be developed as the new treatment for GBM.