title: Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel.
abstract: As pro-inflammatory cytokines and chemokines contribute to the malignancy of many types of human cancer, we examined the anti-inflammatory effect of bisbibenzyls, a diverse bioactive group of naturally occurring compounds. Marchantin M (Mar M) was identified through a screening process of these compounds as a potent anti-inflammatory agent based on its capacity to inhibit LPS-induced IL6, IL1β and CCL2 expression in HUVECs and PBMCs without affecting cell proliferation. Since Mar M has been found to exhibit anticancer activity, we observed that Mar M treatment also resulted in decreases in the expressions of IL6, IL1β and TNFα in metastatic prostate cancer (PCa) cells. This effect was further confirmed in other cancer cell lines that express high level of pro-inflammatory cytokines. Furthermore, inactivation of NF-κB, a critical transcription factor controlling many pro-inflammatory cytokine expressions, was observed in Mar M-treated PCa cells as evidenced by decreased phosphor-p65 and subsequently phosphor-STAT3. Mar M also suppressed phosphorylation of IKBα, an inhibitor of NF-κB in the cytosol. However, reduced phosphor-p65 by Mar M was slightly increased when knockdown of IKBα, suggesting that Mar M may target upstream molecules of IKBα/NF-κB signaling. Finally, treatment with Mar M resulted in more enhanced-sensitivity of PCa cells to docetaxel-induced apoptosis than that of the IL6 blocking. Our study demonstrates the potential of the anti-inflammatory agent Mar M as an adjuvant to improve the efficacy of traditional anticancer agents such as docetaxel.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Niu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Jingti
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Natural Product Chemistry, Shandong University School of Pharmaceutical Sciences, Jinan 250012, China.
authors.forename: Fanghua
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Keli
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, China. Electronic address: lyuanhq@sdu.edu.cn.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Natural Product Chemistry, Shandong University School of Pharmaceutical Sciences, Jinan 250012, China. Electronic address: louhongxiang@sdu.edu.cn.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001632:Bibenzyls / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010647:Phenyl Ethers / Q000494:pharmacology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001632:Bibenzyls; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C000606204:NFKBIA protein, human; D010647:Phenyl Ethers; C498143:RELA protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D043823:Taxoids; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C584935:marchantin M; D000072000:NF-KappaB Inhibitor alpha; D000077143:Docetaxel
keywords: Bisbibenzyls; Cancer; Inflammation; Interleukin 6; Marchantin M