title: Pro-inflammatory effect of a traditional Chinese medicine formula with potent anti-cancer activityin vitroimpedes tumor inhibitory potentialin vivo.
abstract: Medicinal formulas are a part of the complex discipline of traditional Chinese medicine that has been used for centuries in China and East Asia. These formulas predominantly consist of the extracts isolated from herbal plants, animal parts and medicinal minerals. The present study aimed to investigate the impact of 150 formulas, used as non-prescription drugs in China, on the treatment of cancer. A formula was identified, C54, commonly used to treat sore throats, which exhibited marked growth inhibitionin vitro, associated with cell cycle arrest and apoptosis. Cytotoxicity was, in part, due to the ability of C54 to inhibit the expression and function of the transcription factor, Fli-1, leading to marked inhibition of leukemic cell growth in tissue culture. However, when injected into a model of leukemia initiated by Fli-1 activation, C54 only exhibited a limited tumor inhibition. C54 also did not suppress xenograft growth of the breast cancer cell line, MDA-MB-231, orthopedically transplanted into the mammary fat pad of severe combined immunodeficiency (SCID) mice. Notably, splenomegaly and accumulation of inflammatory CD11b+/Gr1+monocytes were observed in the tumors and spleens of C54-treated mice. As inflammation is known to accelerate tumor progression, this immune response may counteract the cell-autonomous effect of C54, and account for its limited tumor inhibitory effectin vivo. Combining C54 with an anti-inflammatory drug may improve the potency of C54 for treatment of certain cancers. The present study has highlighted the complexity of Chinese medicinal compounds and the need to thoroughly analyze their systemic effects at high concentrationsin vivo.
authors.affiliation: School of Pharmaceutical Sciences, Guizhou University, Guiyang, Guizhou 550025, P.R. China; Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Maksym
authors.initials: M
authors.lastname: Plachynta
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Tangjingjun
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Song
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Mu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Luo
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China; Department of Biological Sciences, Guiyang Medical University, Guiyang, Guizhou 550025, P.R. China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Hao
authors.affiliation: Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China; Department of Biological Sciences, Guiyang Medical University, Guiyang, Guizhou 550025, P.R. China.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Ben-David
keywords: Fli-1; apoptosis; cancer progression; inflammation; traditional Chinese medicine drugs