Laboratory studies of berberine used alone and in combination with 1,3-bis (2-chloroethyl) -1-nitrosourea to treat malignant brain tumors
Zhang, R.X.; Dougherty, D.V.; Rosenblum, M.L.
Chinese Medical Journal 103(8): 658-665
1990
ISSN/ISBN: 0366-6999 PMID: 2122945 Document Number: 358944
Berberine was evaluated for antitumor activity against malignant brain tumors. In addition, studies on combination of berberine with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were done. Several experimental approaches were used. In vitro studies were performed on a series of 6 human malignant brain tumor cell lines and rat 9L brain tumor cells (gliosarcoma) by using a colony forming efficiency (CFE) assay. 9L was also evaluated by a sister chromatid exchange (SCE) assay. In addition, in vivo treatment of intracerebral 9L solid brain tumors was analyzed by CFE assay. Berberine used alone at a dose of 150 micrograms/ml showed an average of 91% cell kill (1.08 log kill) for the 6 malignant brain tumor cell lines. On the average, BCNU alone at a dose of 23 microM gave a 43% cell kill (0.24 log kill). Treatment with a combination of berberine and BCNU at 23 microM showed additive effects with an average of 97% cell kill (1.55 log kill). The relative number of SCEs for 9L cells was increased 2.7 times over background following in vitro treatment with 150 micrograms/ml berberine. Following in vivo treatment of animals harboring solid 9L brain tumors with 10 mg/kg of berberine, an 80.9% cell kill (0.69 log kill) was noted. This activity is equivalent to treatment with 1/3 LD10 dose of BCNU (4.44 mg/kg). In vivo combination treatment with berberine and BCNU showed additive cytotoxicity. Using a BCNU-resistant 9L subline (9L-2), treatment with berberine in combination with BCNU also demonstrated additive cytotoxicity. In conclusion, our results indicate that berberine has potent antitumor activity against human and rat malignant brain tumors.