Laboratory studies of berberine used alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea to treat malignant brain tumors

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)