vinorelbine and Neoplasms

Cancer invasion and metastasis are the leading causes of death. The process of metastasis or tumor cell dissemination is still much of a mystery. Emerging evidence has shown that epithelial-mesenchymal transition (EMT) plays a vital role in the progression of malignant tumor including the inducing cell invasion and metastasis as well as promoting drug resistance. Vinorelbine is a traditional chemotherapeutic agent for treatment of lung cancer and breast cancer by the selectivity to mitotic microtubules. The aim of this study was to investigate the effect of vinorelbine on three metastatic cancer cells including lung cancer (H1975), liver cancer (HepG2), and colon cancer (HCT116) cells through inhibition of metastatic abilities and EMT program. Vinorelbine inhibited the cancer cell proliferation by MTT and colony formation assays and inducing G2/M arrest and cell apoptosis via regulation of Bax, Bcl-2, and Bcl-xL. Vinorelbine decrease the migration and invasion ability of the cancer cells by wound healing assay and Tran swell test. The molecular mechanisms of vinorelbine suppressing the metastatic phenotypes of cancer cells through modulation of E-cadherin, N-cadherin, vimentin and transcription factors Snail, MMP-2 and MMP-9. Our results demonstrated that vinorelbine inhibited the cancer cell metastasis through a reduction in metastatic mobility, such as migration, invasion, and the EMT. It provided the evidence that vinorelbine can be used alone or with other agents for treatment of metastatic lung cancer, liver cancer and colon cancer.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colonic Neoplasms; Epithelial-Mesenchymal Transition; G2 Phase Cell Cycle Checkpoints; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Tubulin Modulators; Vinorelbine

Griseofulvin, an antifungal drug, has been shown in recent years to have anti-proliferative activities. We report here the synthesis of new analogs of griseofulvin, substituted in 2' by a sulfonyl group or in 3' by a sulfinyl or sulfonyl group. These compounds exhibit good anti-proliferative activities against SCC114 cells, an oral squamous carcinoma cell line showing pronounced centrosome amplification, and unexpected cytotoxic activities on HCC1937 cells, a triple negative breast cancer cell line resistant to microtubule inhibitors.

Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Griseofulvin; Humans; Neoplasms; Sulfones; Sulfoxides

We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer.

Topics: Animals; Cell Division; Cell Line, Tumor; Cytotoxicity, Immunologic; Drug Resistance, Neoplasm; Hedgehog Proteins; Humans; Indoles; Killer Cells, Natural; Mice; Mitosis; Neoplasms; NIH 3T3 Cells; Tubulin

Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3β,12β,24S-trihydroxy-dammara-20(22)E,25-diene-3-O-β-D-glucopyranoside, 1] and 20(S)-ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were isolated from the alkaline hydrolysate of total saponins of the stems-leaves of Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. All 14 compounds were evaluated for their anti-proliferative activities against two human cancer cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6 exhibited significant inhibitory activity in a concentration-dependent manner against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33μM, respectively, and had comparable IC50 values with those of vinorelbine, a positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential activator of SIRT1. The preliminary structure-activity relationship was also discussed based on the experimental data obtained.

Topics: Antineoplastic Agents, Phytogenic; Cell Proliferation; Enzyme Activation; Ginsenosides; Hep G2 Cells; HL-60 Cells; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Structure; Neoplasms; Panax; Plant Leaves; Plant Stems; Protein Hydrolysates; Saponins; Sirtuin 1

We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway.

Topics: Aniline Compounds; Animals; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Cell Membrane Permeability; Cell Proliferation; Cell Survival; Colchicine; Drug Screening Assays, Antitumor; Guanidines; Hedgehog Proteins; Humans; M Phase Cell Cycle Checkpoints; Mice; Molecular Docking Simulation; Neoplasms; Polymerization; Protein Binding; Pyrroles; Signal Transduction; Structure-Activity Relationship; Tubulin; Tubulin Modulators

A new, practical and efficient method for the synthesis of anhydrovinblastine AVBL (1f) by oxidative coupling of vindoline and catharanthine in the presence of ceric ammonium nitrate (CAN) was developed. Under the optimized reaction conditions, we synthesized a new series of amide anhydrovinblastine analogs substituted at the vindoline moiety of C-23 site and, evaluated for their proliferation inhibition against HeLa cell. The aryl-substituted derivatives showed loss of potency, while alkyl-substituted derivatives retained some of its cytotoxic potency. The iso-butylamide compound 10b and 2-furancorboxamide compound 18b displayed a similar cytotoxic potency compared to the positive control AVBL.

Topics: Antineoplastic Agents; Binding Sites; Cell Proliferation; Cerium; Chemistry, Pharmaceutical; Circular Dichroism; Drug Design; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Hydrogen-Ion Concentration; Inhibitory Concentration 50; Models, Chemical; Neoplasms; Oxygen; Time Factors; Vinblastine; Vinca Alkaloids