title: Inhibiting MDSC differentiation from bone marrow with phytochemical polyacetylenes drastically impairs tumor metastasis.
abstract: Myeloid-derived suppressor cells (MDSCs) are implicated in the promotion of tumor metastasis by protecting metastatic cancerous cells from immune surveillance and have thus been suggested as novel targets for cancer therapy. We demonstrate here that oral feeding with polyacetylenic glycosides (BP-E-F1) from the medicinal plant Bidens pilosa effectively suppresses tumor metastasis and inhibits tumor-induced accumulation of granulocytic (g) MDSCs, but does not result in body weight loss in a mouse mammary tumor-resection model. BP-E-F1 is further demonstrated to exert its anti-metastasis activity through inhibiting the differentiation and function of gMDSCs. Pharmacokinetic and mechanistic studies reveal that BP-E-F1 suppresses the differentiation of gMDSCs via the inhibition of a tumor-derived, G-CSF-induced signaling pathway in bone marrow cells of test mice. Taken together, our findings suggest that specific plant polyacetylenic glycosides that target gMDSC differentiation by communicating with bone marrow cells may hence be seriously considered for potential application as botanical drugs against metastatic cancers.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Wei
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, ROC, Taiwan.
authors.forename: Sheng-Yen
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, ROC, Taiwan.
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Lan
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsiao
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Yet-Ran
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, ROC, Taiwan.
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
mesh_terms: D000818:Animals; D031176:Bidens / Q000737:chemistry; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology / Q000187:drug effects*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D064209:Phytochemicals / Q000494:pharmacology*; D053279:Polyynes / Q000494:pharmacology*
chemical_list: D064209:Phytochemicals; D016179:Granulocyte Colony-Stimulating Factor; D053279:Polyynes