renieramycin-m has been researched along with Lung-Neoplasms* in 9 studies
9 other study(ies) available for renieramycin-m and Lung-Neoplasms
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22-O-(N-Boc-L-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial-mesenchymal transition in human lung cancer cells.
The incidence of metastasis stage crucially contributes to high recurrence and mortality rate in lung cancer patients. Unfortunately, no available treatment inhibits migration, a key metastasis process in lung cancer. In this study, the effect of 22-O-(N-Boc-L-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated from Xestospongia sp., on migratory behavior of human lung cancer cells was investigated. Following 24 h of treatment, 22-Boc-Gly-RM at non-toxic concentrations (0.5-1 μM) effectively restrained motility of human lung cancer H460 cells assessed through wound healing, transwell migration, and multicellular spheroid models. The capability to invade through matrix component was also repressed in H460 cells cultured with 0.1-1 µM 22-Boc-Gly-RM. The dose-dependent reduction of phalloidin-stained actin stress fibers corresponded with the downregulated Rac1-GTP level presented via western blot analysis in 22-Boc-Gly-RM-treated cells. Treatment with 0.1-1 μM of 22-Boc-Gly-RM obviously caused suppression of p-FAK/p-Akt signal and consequent inhibition of epithelial-to-mesenchymal transition (EMT), which was evidenced with augmented level of E-cadherin and reduction of N-cadherin expression. The alteration of invasion-related proteins in 22-Boc-Gly-RM-treated H460 cells was indicated by the diminution of matrix metalloproteinases (MT1-MMP, MMP-2, MMP-7, and MMP-9), as well as the upregulation of tissue inhibitors of metalloproteinases (TIMP), TIMP2, and TIMP3. Thus, 22-Boc-Gly-RM is a promising candidate for anti-metastasis treatment in lung cancer through inhibition of migratory features associated with suppression on EMT. Topics: Cell Line, Tumor; Cell Movement; Cell Survival; Epithelial-Mesenchymal Transition; Esters; Glycine; Humans; Lung Neoplasms; Tetrahydroisoquinolines | 2021 |
Chemistry of Renieramycins. Part 19: Semi-Syntheses of 22-
Two new series of synthetic renieramycins including 22- Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Survival; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Lung Neoplasms; Molecular Structure; Structure-Activity Relationship; Tetrahydroisoquinolines | 2020 |
Chemistry of Renieramycins. 17. A New Generation of Renieramycins: Hydroquinone 5-O-Monoester Analogues of Renieramycin M as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.
A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC Topics: Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cytotoxins; Humans; Hydroquinones; Lung Neoplasms; Molecular Structure; Tetrahydroisoquinolines; Thailand; Xestospongia | 2017 |
Apoptosis-inducing Effect of Hydroquinone 5-
A newly-synthesized derivative of renieramycin M (RM), an anticancer lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O-cinnamoyl ester (CIN-RM), was investigated here for its activity against non-small cell lung cancer cells.. Cytotoxicity effects of CIN-RM and RM on H292 lung cancer cells were determined by the MTT assay. We also investigated the mechanism of CIN-RM-mediated apoptosis and mechanism of action of this compound by western blotting.. CIN-RM showed more potent cytotoxicity than its parental compound (RM) against H292 lung cancer cells. At concentrations of 15-60 μM, CIN-RM significantly induced apoptosis by increasing expression of apoptosis-inducing factor (AIF) and activation of caspase-3 and -9. For up-stream mechanism, CIN-RM mediated apoptosis through a p53-dependent mechanism, that consequently down-regulated anti-apoptotic B-cell lymphoma 2 (BCL2), while increasing the level of pro-apoptotic BCL2-associated X (BAX). In addition, phosphorylation of pro-survival protein AKT was found to be dramatically reduced.. This study revealed the potential of CIN-RM for apoptosis induction and in the development of a novel anticancer agent. Topics: Apoptosis; Apoptosis Inducing Factor; Carcinoma, Non-Small-Cell Lung; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Humans; Hydroquinones; Lung Neoplasms; Signal Transduction; Tetrahydroisoquinolines | 2017 |
Renieramycin M Attenuates Cancer Stem Cell-like Phenotypes in H460 Lung Cancer Cells.
Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess self-renewal and differentiation capacities. CSCs contribute to drug-resistance, cancer recurrence and metastasis, thus development of CSC-targeted therapeutic strategies has recently received significant attention in cancer research. In this study, the potential efficacy of renieramycin M (RM) isolated from the sponge Xestospongia species, was examined against lung CSCs.. Colony and spheroid formation assays, as well as western blotting analysis of lung CSC protein markers were employed to determine the CSC-like phenotypes of H460 lung cancer cells after treatment with RM at non-toxic concentrations.. RM treatment reduced significantly colony and spheroid formation of H460 cells. Moreover, the CSC markers CD133, CD44 and ALDH1A1 of CSC-enriched H460 cells were reduced significantly following RM treatment.. RM could be a potent anti-metastatic agent by suppressing lung CSC-like phenotypes in H460 cells. Topics: AC133 Antigen; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Biomarkers, Tumor; Blotting, Western; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Humans; Hyaluronan Receptors; Lung Neoplasms; Neoplastic Stem Cells; Phenotype; Retinal Dehydrogenase; Spheroids, Cellular; Tetrahydroisoquinolines; Xestospongia | 2017 |
Renieramycin M Sensitizes Anoikis-resistant H460 Lung Cancer Cells to Anoikis.
Anoikis resistance plays a crucial role in the promotion of survival of circulating tumor cells. This study aimed to evaluate the mechanistic pathways of anoikis resistance in human lung cancer cells and test the possible therapeutic effect of renieramycin M (RM) from the sponge Xestospongia sp. in conversion of anoikis resistance.. Anoikis-resistant H460 (AR_H460) lung cancer cells in a detached condition were treated with RM at subtoxic concentrations for 24 h. Cell viability, cell morphology, and expression of the proteins involved in survival and apoptotic pathways were determined.. Anoikis resistance in H460 cells is mediated through the up-regulation of survival and anti-apoptotic proteins, namely phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), B-cell lymphoma-2 (BCL2), and myeloid cell leukemia-1 (MCL1). RM significantly reduced cell viability and inhibited spontaneous aggregation of AR_H460 cells. Western blot analysis revealed that RM suppressed the levels of survival proteins p-ERK and p-AKT and anti-apoptotic proteins BCL2 and MCL1.. RM is a potential anti-metastatic agent by sensitizing anoikis-resistant lung cancer cells to anoikis by the suppression of anoikis-resistance mechanisms. Topics: Anoikis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Survival; Extracellular Signal-Regulated MAP Kinases; Humans; Lung Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Tetrahydroisoquinolines; Up-Regulation | 2016 |
Bishydroquinone Renieramycin M Induces Apoptosis of Human Lung Cancer Cells Through a Mitochondria-dependent Pathway.
Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells.. HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively. The key molecular markers of mitochondrial apoptosis pathway were determined by western blot analysis.. HQ-RM exhibited stronger cytotoxicity than RM. HQ-RM reduced vitality of lung cancer cells in a dose-dependent manner. Nuclear staining assay indicated that apoptotic cell death was the main mechanism of toxicity caused by HQ-RM. Protein analysis revealed that HQ-RM-mediated apoptosis involved the increase of pro-apoptotic B-cell lymphoma 2 associated X (BAX) protein, and the decrease of anti-apoptosis myeloid cell leukemia 1 (MCL1) and B-cell lymphoma 2 (BCL2) proteins. Moreover, caspase-9 and -3 and Poly (ADP-ribose) polymerase (PARP) were dramatically cleaved in response to HQ-RM treatment.. HQ-RM has highly potent anticancer activity, greater than its parental RM, and induces lung cancer cell apoptosis through a mitochondrial apoptosis caspase-dependent mechanism. This information benefits the development of this compound for cancer therapy. Topics: Apoptosis; Cell Line, Tumor; Humans; Lung Neoplasms; Mitochondria; Tetrahydroisoquinolines | 2016 |
Replacement of a quinone by a 5-O-acetylhydroquinone abolishes the accidental necrosis inducing effect while preserving the apoptosis-inducing effect of renieramycin M on lung cancer cells.
Renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the marine sponge Xestospongia sp., has been reported to possess promising anticancer effects. However, its accidental necrosis inducing effect has limited further development due to concerns of unwanted toxicity. The presence of two quinone moieties in its structure was demonstrated to induce accidental necrosis and increase reactive oxygen species (ROS) levels. Therefore, one quinone of 1 was modified to produce the 5-O-acetylated hydroquinone derivative (2), and 2 dramatically reduced the accidental necrosis inducing effect while preserving the apoptosis-inducing effect of parent 1 on lung cancer H23 cells. Addition of the antioxidant N-acetylcysteine suppressed the accidental necrosis mediated by 1, suggesting that its accidental necrosis inducing effect was ROS-dependent. The fluorescent probe dihydroethidium revealed that the accidental necrosis mediated by 1 was due to its ability to generate intracellular superoxide anions. Interestingly, the remaining quinone in 2 was required for its cytotoxicity, as the 5,8,15,18-O-tetraacetylated bishydroquinone derivative (3) exhibited weak cytotoxicity compared to 1 and 2. The present study demonstrates a simple way to eliminate the undesired accidental necrosis inducing effect of substances that may be developed as improved anticancer drug candidates. Topics: Acetylcysteine; Alkaloids; Antineoplastic Agents; Apoptosis; Humans; Hydroquinones; Lung Neoplasms; Molecular Structure; Necrosis; Structure-Activity Relationship; Tetrahydroisoquinolines; Tumor Suppressor Protein p53 | 2013 |
Anticancer and antimetastatic activities of Renieramycin M, a marine tetrahydroisoquinoline alkaloid, in human non-small cell lung cancer cells.
Renieramycin M, has been shown to exhibit promising anticancer activity against some cancer cell lines; however, the underlying mechanism remains unknown.. Renieramycin M was isolated from the blue sponge Xestospongia sp. Anticancer and antimetastatic activities of renieramycin M were investigated in human non-small cell lung cancer cells.. Renieramycin M treatment caused p53 activation, which subsequently down-regulated anti-apoptotic MCL-1 and BCL-2 proteins, while the level of pro-apoptotic BAX protein was not altered. The subtoxic concentrations of renieramycin M significantly decreased invasion and migration abilities of cancer cells. In addition, this compound showed a strong inhibitory effect on anchorage-independent growth of the cells.. These results reveal that renieramycin M induced lung cancer cells apoptosis through p53-dependent pathway and the compound may inhibit progression and metastasis of lung cancer cells. Topics: Alkaloids; Animals; Anoikis; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Adhesion; Cell Movement; Cell Proliferation; Colony-Forming Units Assay; Humans; Lung Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Porifera; Proto-Oncogene Proteins c-bcl-2; Tetrahydroisoquinolines; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Wound Healing | 2011 |