Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts

Mandai, Hiroki; Omori, Kazuhiro; Yamamoto, Daisuke; Tsumura, Takehiko; Murota, Kyouta; Yamamoto, Satoshi; Mitsudo, Koichi; Ibaragi, Soichiro; Sasaki, Akira; Maéda, Hiroshi; Takashiba, Shogo; Suga, Seiji

doi:10.1016/j.bmc.2014.07.047

Cited by 21 publications

(26 citation statements)

References 42 publications

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“…Proteasome inhibitiors such as botezomib, induce apoptosis and cell-cycle arrest, and have been approved for the treatment of cancers (30). Notably, the inhibition of ERK or AKT signaling is often observed in terrein-treated cells even in the absence of apoptosis (7,31,32) and the inhibition of ERK and Akt phosphorylation has been reported following proteasome inhibition (33). One hypothesis is that the differential outcome of terrein treatment on various cell lines may be due to their susceptibility to inhibition of the proteasome.…”

Section: Discussionmentioning

confidence: 99%

Terrein inhibits migration of human breast cancer cells via inhibition of the Rho and Rac signaling pathways

et al. 2018

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Breast cancer is the most common cancer in women worldwide. Progression and aggressiveness of breast cancer is usually associated with its migration and invasion abilities. Recently, natural products with potential anticancer activity have become attractive candidates for alternative treatment of cancer. A fungal metabolite, terrein, isolated from the Aspergillus terreus has been revealed to exhibit selective anticancer activity; although this molecule has a variety of biological activities. The inhibitory effect on cell proliferation in hepatoma, keratinocytes, and lung cancer cells was due to cell cycle arrest without induction of apoptosis. In contrast, its effects on cervical and breast cancer cells were mediated through activation of the apoptotic process. However, the effect of terrein on cell migration and invasion has not been explored. In the present study we analyzed the molecular effects of terrein on cell adhesion, cell migration, and cell invasion using two breast cancer cell lines, MCF-7 and MDA-MB-231, which exhibit different levels of invasiveness. Terrein induced apoptosis in both breast cancer cell lines in a dose-dependent manner. In addition, at a non-toxic concentration terrein exhibited a weak inhibition of cell adhesion, using either fibronectin or type IV collagen as substrates. Notably, terrein significantly inhibited both the migration and invasion abilities of MDA-MB-231 cells at the same non-toxic concentration. A marked decrease in MMP-2 and MMP-9 transcripts, as evaluated by real-time PCR, confirmed the anti-invasion effect of terrein at the transcriptional level. Western blot analyses revealed that terrein treatment suppressed RhoB expression and reduced Rac1 phosphorylation, leading to Rho GTPase inhibition. In addition, terrein-treated MCF-7 and MDA-MB-231 cells both displayed a scattered pattern of migration, suggesting that the suppression of RhoB and Rac1 disturbed the collective migration processes of breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Terrein inhibits migration of human breast cancer cells via inhibition of the Rho and Rac signaling pathways

et al. 2018

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“…The whole process included cyclization, Horner-Wadsworth-Emmons, and deprotection of bis-t-butyldimethylsilyl (bis-TBS) group as shown in Scheme 22 [221]. Chemically, secalonic acid D (105) is the chiral dimeric natural product of ergochrome xanthone [213].…”

Section: Terreinmentioning

confidence: 99%

“…The whole process included cyclization, Horner-Wadsworth-Emmons, and deprotection of bis-t-butyldimethylsilyl (bis-TBS) group as shown in Scheme 22 [221]. Figure 22) is a diketomorpholine isolated from the marine fungus Aspergillus sp.…”

Section: Terreinmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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“…In development of periodontal disease, HGFs play critical roles 45 and overproduction of inflammatory mediators are the primary cause of inflammatory responses and tissue degradation. 46 A previous study by the authors confirmed that stimulation of HGFs with Pg LPS could induce production of IL-6, IL-1b, and TNFa.…”

Section: Figurementioning

confidence: 99%

Metformin Inhibits Porphyromonasgingivalis Lipopolysaccharide‐Influenced Inflammatory Response in Human Gingival Fibroblasts via Regulating Activating Transcription Factor‐3 Expression

Kang

Wang

et al. 2017

Journal of Periodontology

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Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts

Cited by 21 publications

References 42 publications

Terrein inhibits migration of human breast cancer cells via inhibition of the Rho and Rac signaling pathways

Terrein inhibits migration of human breast cancer cells via inhibition of the Rho and Rac signaling pathways

Marine Natural Products as Models to Circumvent Multidrug Resistance

Metformin Inhibits Porphyromonasgingivalis Lipopolysaccharide‐Influenced Inflammatory Response in Human Gingival Fibroblasts via Regulating Activating Transcription Factor‐3 Expression

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