Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

Charupant, Kornvika; Suwanborirux, Khanit; Daikuhara, Naomi; Yokoya, Masashi; Ushijima-Sugano, Rie; Kawai, Takatoshi; Owa, Takashi; Saito, Naoki

doi:10.3390/md7040483

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…This is contrary to the report of Halim et al [8] and is probably due to the difference between the RM concentration (≥5 µM vs. 6.25 nM) used in the study. Moreover, RM was 10-fold more sensitive in p53 mutant MDA-MB-435 melanoma than in p53 wild type HCT116 colon carcinoma [2], supporting the hypothesis that p53 may not be required in the cytotoxicity of RM.…”

Section: Resultsmentioning

confidence: 83%

“…Renieramycin M (RM) is a KCN-stabilized tetrahydroisoquinoline purified from the blue sponge Xestospongia sp. (Figure 1), with nanomolar IC 50 s against the colon, lung, melanoma, and pancreatic cancer cells [2,3,4,5,6,7]. RM induces apoptosis and inhibits invasion and migration in non-small cell lung cancer cells (NSCLC) in vitro, making it a potential antimetastatic agent [8].…”

Section: Introductionmentioning

confidence: 99%

“…This warrants further investigation on the potential clinical utility of RM. A transcriptional structure–activity relationship (SAR) study and molecular network profiling revealed that RM and the ecteinascidin class of compounds induce apoptosis via a common pathway in the colon, breast [2], and glioblastoma cells [9]. Et-743 was reported to have a sequence-dependent synergistic effect with paclitaxel in breast carcinoma [10], and with doxorubicin in soft tissue sarcoma in vitro [11].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells

et al. 2019

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Renieramycin M (RM) is a KCN-stabilized tetrahydroisoquinoline purified from the blue sponge Xestospongia sp., with nanomolar IC50s against several cancer cell lines. Our goal is to evaluate its combination effects with doxorubicin (DOX) in estrogen receptor positive MCF-7 breast cancer cells. MCF-7 cells were treated simultaneously or sequentially with various combination ratios of RM and DOX for 72 h. Cell viability was determined using the MTT assay. Synergism or antagonism was determined using curve-shift analysis, combination index method and isobologram analysis. Synergism was observed with pharmacologically achievable concentrations of DOX when administered simultaneously, but not sequentially. The IC95 values of RM and DOX after combination were reduced by up to four-fold and eight-fold, respectively. To gain insights on the mechanism of synergy, real-time profiling, cell cycle analysis, apoptosis assays, and transcriptome analysis were conducted. The combination treatment displayed a similar profile with DNA-damaging agents and induced a greater and faster cell killing. The combination treatment also showed an increase in apoptosis. DOX induced S and G2/M arrest while RM did not induce significant changes in the cell cycle. DNA replication and repair genes were downregulated commonly by RM and DOX. p53 signaling and cell cycle checkpoints were regulated by DOX while ErbB/PI3K-Akt, integrin and focal adhesion signaling were regulated by RM upon combination. Genes involved in cytochrome C release and interferon gamma signaling were regulated specifically in the combination treatment. This study serves as a basis for in vivo studies and provides a rationale for using RM in combination with other anticancer drugs.

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Section: Resultsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells

et al. 2019

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“…It is noteworthy that quinoline-2-carboxylic acid amide derivative of saframycin A (QAD, 4) was shown to possess single-digit picomolar potency against three human sarcoma cell lines 100 times more potent than Et-743 [24]. On the other hand, the ester side chain structure of renieramycin M was also found to have a critical impact on its antitumor activities [25]. We envisioned that 4H-chromene-2-carboxylic acid ester derivatives of renieramycin M (6) might be of some use for the structural-activity relationship studies of this antitumor antibiotic marine natural product.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Studies on Potent Marine Drugs: Synthesis and the Crystal Structure of 6‐tert‐butyl‐4‐phenyl‐4H‐chromene‐2‐carboxylic Acid

Wang

Luo

et al. 2013

Journal of Chemistry

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4H-Chromene-2-carboxylic acid ester derivatives of renieramycin M might be of use for the structural-activity relationship studies of antitumor antibiotic tetrahydroisoquinoline natural products. Accordingly, 6-tert-butyl-4-phenyl-4H-chromene-2-carboxylic acid, one key intermediate, was synthesized via the condensation of (3E)-2-oxo-4-phenylbut-3-enoate methyl ester with 4-tert-butylphenol in the presence of AuCl3/3AgOTf (5 mol%), followed by cyclodehydration and aqueous hydrolysis. The product was unambiguously shown to the 4H-chromene-2-carboxylic acid by spectroscopy and X-ray crystallographic analysis. A packing diagram of the crystal structure shows that aromaticπ-stacking interactions and O–H⋯O hydrogen bond stabilize the structure in the solid.

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“…and jorunnamycin C from Jorunnafunebris , both having promising anticancer activity with IC 50 values in the nanomolar range. 12 In this paper, we chose two typical isoquinolines, 4-hydroxyisoquinoline ( 1 ) and 6-hydroxyisoquinoline ( 2 ), to test whether Rdc2 could chlorinate this important type of molecule. As shown in Fig.…”

mentioning

confidence: 99%

Specific chlorination of isoquinolines by a fungal flavin-dependent halogenase

Zeng

Lytle

Gage

et al. 2013

Bioorganic & Medicinal Chemistry Letters

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Rdc2 is the first flavin-dependent halogenase identified from fungi. Based on the reported structure of the bacterial halogenase CmlS, we have built a homology model for Rdc2. The model suggests an open substrate binding site that is capable of binding the natural substrate, monocillin II, and possibly other molecules such as 4-hydroxyisoquinoline (1) and 6-hydroxyisoquinoline (2). In vitro and in vivo halogenation experiments confirmed that 1 and 2 can be halogenated at the position ortho to the hydroxyl group, leading to the synthesis of the chlorinated isoquinolines 1a and 2a, respectively, which further expands the spectrum of identified substrates of Rdc2. This work revealed that Rdc2 is a useful biocatalyst for the synthesis of various halogenated compounds.

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Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

Cited by 14 publications

References 24 publications

Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells

Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells

Synthetic Studies on Potent Marine Drugs: Synthesis and the Crystal Structure of 6‐tert‐butyl‐4‐phenyl‐4H‐chromene‐2‐carboxylic Acid

Specific chlorination of isoquinolines by a fungal flavin-dependent halogenase

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