Protective Effect of the Natural Product, Chaetoglobosin K, on Lindane- and Dieldrin-induced Changes in Astroglia: Identification of Activated Signaling Pathways

Sidorova, Tatyana S.; Matesic, Diane F.

doi:10.1007/s11095-007-9487-x

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…ChK prevents tumor promoter-induced inhibition of cell-cell communication in non-transformed cells, as previously reported [16]. Figure 1A shows that preincubation of cells with 5 μM ChK, followed by 30 min incubation with 10 μM dieldrin or 50 μM lindane, resulted in a greater number of dye-transfer fluorescent cells than treatment with dieldrin or lindane alone (p<0.05).…”

Section: Resultssupporting

confidence: 80%

A Cell-Cell Communication Marker for Identifying Targeted Tumor Therapies

Matesic¹,

Ali²,

Sidorova³

et al. 2014

CBC

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Cell-cell communication through gap junctions is aberrant or absent in a majority of human cancer cells, compared to cells in corresponding normal tissues. This and other evidence has led to the hypothesis that gap junction channels, comprised of connexin proteins, are important in growth control and cancer progression. The major goal of this ongoing study was to identify bioactive compounds that specifically upregulate gap junction channel-mediated cell-cell communication as potential anti-tumor therapies. Control of cell-cell communication is linked to growth regulatory intracellular signaling pathways; we therefore further aimed to identify signaling pathways modulated by these compounds in order to assess their potential as targeted anti-tumor therapies. Compounds were screened for their ability to upregulate gap junction-mediated cell-cell communication by using a fluorescent dye transfer assay to measure cell-cell communication between tumor promoter-treated astroglial cells or ras-transformed epithelial cells. Western blotting using connexin-specific and phosphorylation site-specific antibodies was used to monitor phosphorylation changes in signaling pathway proteins. Our results identified three compounds that upregulate gap junction-mediated cell-cell communication in our screening assays, chaetoglobosin K(ChK), 4-phenyl-3-butenoic acid (PBA) and the methyl ester of PBA (PBA-Me). Further analyses demonstrated that in tumorigenic cells, ChK downregulates phosphorylation of Akt kinase, an enzyme in the PI3-kinase signaling pathway that is found to be upregulated in a number of human cancers, on a key activation site. However, ChK did not inhibit PI-3 kinase in vitro as did the classic PI-3 kinase inhibitor, Wortmannin. PBA and PBA-Me were found to upregulate phosphorylation of p38 MAPK on a key activation site in tumorigenic cells, which is downregulated in several human cancer cell types. ChK and PBA also decreased activation of SAPK/JNK, another kinase found to be upregulated in a number of human cancers. These studies highlight the potential of monitoring gap junction intercellular communication for identifying experimental anti-tumor compounds.

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Section: Resultssupporting

confidence: 80%

A Cell-Cell Communication Marker for Identifying Targeted Tumor Therapies

Matesic¹,

Ali²,

Sidorova³

et al. 2014

CBC

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“…erefore, it might be an mTOR inhibitor [33]. Moreover, administration of compound 15 to astroglial cell line can prevent and reverse the inhibition of lindane and dieldrin to gap junction-mediated communication, by stabilizing and reappearing the connexin 43 P2 phosphoform and activating the Akt/GSK-3β pathway [35][36][37].…”

Section: Antitumor Activitymentioning

confidence: 99%

Bioactivities and Future Perspectives of Chaetoglobosins

Chen

Zhang

Guo

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Chaetoglobosins belonging to cytochalasan alkaloids represent a large class of fungal secondary metabolites. To date, around 100 chaetoglobosins and their analogues have been isolated and identified over the years from a variety of fungi, mainly from the fungus Chaetomium globosum. Studies have found that chaetoglobosins possess a broad range of biological activities, including antitumor, antifungal, phytotoxic, fibrinolytic, antibacterial, nematicidal, anti-inflammatory, and anti-HIV activities. This review will comprehensively summarize the biological activities and mechanisms of action of nature-derived chaetoglobosins.

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“…Chaetoglobosin K (ChK) was first isolated from the fungus Diplodia macrospora in 1980 and was found to have inhibitory and toxic effects on plant growth [9]. Recently, this compound was shown to prevent organochlorine-induced inhibition of gap junctional communication in astrocytes and astroglial cells [10,11], inhibit both Akt and JNK phosphorylation at key activation sites in ras-transformed epithelial cells and human lung carcinoma cells [12], and effectively inhibit angiogenesis through downregulation of vascular epithelial growth factor (VEGF)-binding hypoxia-inducible factor 1α (HIF-1α) in ovarian cancer cells [13]. …”

Section: Introductionmentioning

confidence: 99%

Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells

Gao

Rankin

et al. 2015

Cancer Letters

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Adverse side effects and acquired resistance to conventional platinum based chemotherapy have become major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs. Chaetoglobosin K (ChK) was shown to have a more potent growth inhibitory effect than cisplatin on two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and was less cytotoxic to a normal ovarian cell line, IOSE-364, than to the cancer cell lines. Hoechst 33342 staining and Flow cytometry analysis indicated that ChK induced preferential apoptosis and G2 cell cycle arrest in both ovarian cancer cells with respect to the normal ovarian cells. ChK induced apoptosis through a p53-dependent caspase-8 activation extrinsic pathway, and caused G2 cell cycle arrest via cyclin B1 by increasing p53 expression and p38 phosphorylation in OVCAR-3 and A2780/CP70 cells. DR5 and p21 might play an important role in determining the sensitivity of normal and malignant ovarian cells to ChK. Based on these results, ChK would be a potential compound for treating platinum-resistant ovarian cancer.

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Protective Effect of the Natural Product, Chaetoglobosin K, on Lindane- and Dieldrin-induced Changes in Astroglia: Identification of Activated Signaling Pathways

Abstract: ChK's protective effects, both preventative and reversal, on lindane and dieldrin inhibition of gap junction-mediated communication are associated with stabilization and reappearance of the connexin 43 P2 phosphoform and may be mediated by the Akt pathway.

Cited by 7 publications

References 39 publications

A Cell-Cell Communication Marker for Identifying Targeted Tumor Therapies

A Cell-Cell Communication Marker for Identifying Targeted Tumor Therapies

Bioactivities and Future Perspectives of Chaetoglobosins

Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells

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