renieramycin-m and Carcinoma--Non-Small-Cell-Lung

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

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

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

Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was evaluated. Preliminary study of the structure-cytotoxicity relationship revealed that the ester part containing a nitrogen-heterocyclic ring elevated the cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl) ester 6a is the most potent compound (IC50 1.1 and 1.6 nM), exhibiting 21-fold and 5-fold increases in cytotoxicity against the H292 and H460 NSCLC cell lines, respectively, relative to renieramycin M (1), the major cytotoxic bistetrahydroisoquinolinequinone alkaloid of the Thai blue sponge Xestospongia sp.

Topics: Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Screening Assays, Antitumor; Humans; Isoquinolines; Marine Biology; Molecular Structure; Porifera; Quinolones; Structure-Activity Relationship; Tetrahydroisoquinolines; Thailand

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