Novel 2‐Substituted Quinolin‐4‐yl‐benzenesulfonate Derivatives: Synthesis, Antiproliferative Activity, and Inhibition of Cellular Tubulin Polymerization

Kakadiya, Rajesh; Wu, Yichen; Dong, Honglin; Kuo, Hsiao-Hui; Yih, Ling-Huei; Chou, Ting‐Chao; Su, Te‐Jen

doi:10.1002/cmdc.201100121

Cited by 13 publications

(6 citation statements)

References 43 publications

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“…To validate the inhibitory effects of mdivi-1 on tubulin polymerization in MDA-MB-231 cells, we performed a cellular tubulin polymerization assay, as previously described 45 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Association of the drug to tubulin reduces the fluorescence emission. The affinity of mdivi-1 to tubulin was thus measured by detecting the emission spectrum of the intrinsic tryptophan fluorescence of tubulin, according to procedures described previously 45 . The reductions of fluorescence intensity at 355 nm at varying mdivi-1 concentrations were calculated, and the values were plotted on a double reciprocal plot.…”

Section: Methodsmentioning

confidence: 99%

“…To probe the effects of mdivi-1 on cellular tubulin polymerization, MDA-MB-231 cells were treated with mdivi-1 as indicated. Cells were then lysed and centrifuged as previously described 45 , and the polymerized tubulin fraction (in the pellet) and the soluble free tubulin fraction (in the supernatant) were subjected to western blotting analysis. Lysate from Ro-3306-blocked-and-released mitotic MDA-MB-231 cells, obtained as described above, was used as a control.…”

Section: Methodsmentioning

confidence: 99%

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Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells

Fang,

Kuo,

Yuan

et al. 2021

Cell Death Discov.

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Taxol is a first-line chemotherapeutic for numerous cancers, including the highly refractory triple-negative breast cancer (TNBC). However, it is often associated with toxic side effects and chemoresistance in breast cancer patients, which greatly limits the clinical utility of the drug. Hence, compounds that act in concert with taxol to promote cytotoxicity may be useful to improve the efficacy of taxol-based chemotherapy. In this study, we demonstrated that mdivi-1, a putative inhibitor of mitochondrial fission protein Drp1, enhances the anticancer effects of taxol and overcomes taxol resistance in a TNBC cell line (MDA-MB-231). Not only did mdivi-1 induce mitotic spindle abnormalities and mitotic arrest when used alone, but it also enhanced taxol-induced antimitotic effects when applied in combination. In addition, mdivi-1 induced pronounced spindle abnormalities and cytotoxicity in a taxol-resistant cell line, indicating that it can overcome taxol resistance. Notably, the antimitotic effects of mdivi-1 were not accompanied by prominent morphological or functional alterations in mitochondria and were Drp1-independent. Instead, mdivi-1 exhibited affinity to tubulin at μM level, inhibited tubulin polymerization, and immediately disrupted spindle assembly when cells entered mitosis. Together, our results show that mdivi-1 associates with tubulin and impedes tubulin polymerization, actions which may underlie its antimitotic activity and its ability to enhance taxol cytotoxicity and overcome taxol resistance in MDA-MB-231 cells. Furthermore, our data imply a possibility that mdivi-1 could be useful to improve the therapeutic efficacy of taxol in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells

Fang,

Kuo,

Yuan

et al. 2021

Cell Death Discov.

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“…The cytotoxicity of the test compounds was determined by counting viable cell numbers with methylthiazol tetrazolium (WST-8) (Cell Count Kit 8; Dojindo Molecular Technologies, Inc.), as described previously [46]. The compound concentration that reduced cell growth by 50% (IC 50 ) was determined based on the dose–effect relationships of six concentrations from three to six independent experiments, using GraphPad PRISM v5.0 (GraphPad, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Derivatives of 6-cinnamamido-quinoline-4-carboxamide impair lysosome function and induce apoptosis

Kuo

Kakadiya

et al. 2016

Oncotarget

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Autophagy is a lysosomal degradative process that protects cancer cells from multiple types of stress. In this study, we synthesized a series of derivatives of 6-cinnamamido-quinoline-4-carboxamide (CiQ), and investigated their effects on the proliferation and autophagy of cancer cells in vitro. These derivatives effectively inhibited the proliferation of a broad spectrum of cancer cell lines. Further study revealed that CiQ derivatives may induce autophagy and result in disruption of autophagy propagation. Consequently, these derivatives triggered massive apoptosis, as evidenced by caspase-9 activation and PARP cleavage. Blockage of autophagy by depletion of autophagy related gene ATG5 or BECN1 considerably alleviated CiQ-induced cell death, indicating that autophagy may mediate CiQ-induced cell death. Furthermore, treatment with CiQ derivatives increased lysosome membrane permeability (LMP) and enhanced accumulation of ubiquitinated proteins, which collectively indicate impaired lysosome function. In addition, treatment of cells with CiQ derivatives activated extracellular signal-regulated kinase (ERK); abrogation of ERK activation, either by treating cells with U0126, an inhibitor of mitogen-activated protein/ERK kinase 1 (MEK1), or by ectopically overexpressing a dominant-negative MEK1, significantly reduced CiQ derivative-induced LMP, LC3 and p62 accumulation, and cytotoxicity. These results indicate that CiQ derivatives activate ERK and disrupt lysosome function, thereby altering autophagic flux and resulting in apoptotic cell death.

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“…The different numbers in the figures refer to absorption peaks described in Additional file 2, Table S1 and Additional file 3, Table S2. According to the approach of Tillmann [46], Rana et al [47] and Nuopponen et al [41] the first eight highest peaks were assigned in the factor loading for PC1 (a), PC2 (b), PC3 (c), and PC4 (d), respectively. PC1, PC2, PC3, and PC4 of the "lignin set" (black line) explained 68.7%, 22.2%, 6.8%, and 2.3% of the variation respectively.…”

Section: Supplementary Materialsmentioning

confidence: 99%

FTIR-ATR-based prediction and modelling of lignin and energy contents reveals independent intra-specific variation of these traits in bioenergy poplars

2011

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BackgroundThere is an increasing demand for renewable resources to replace fossil fuels. However, different applications such as the production of secondary biofuels or combustion for energy production require different wood properties. Therefore, high-throughput methods are needed for rapid screening of wood in large scale samples, e.g., to evaluate the outcome of tree breeding or genetic engineering. In this study, we investigated the intra-specific variability of lignin and energy contents in extractive-free wood of hybrid poplar progenies (Populus trichocarpa × deltoides) and tested if the range was sufficient for the development of quantitative prediction models based on Fourier transform infrared spectroscopy (FTIR). Since lignin is a major energy-bearing compound, we expected that the energy content of wood would be positively correlated with the lignin content.ResultsLignin contents of extractive-free poplar wood samples determined by the acetyl bromide method ranged from 23.4% to 32.1%, and the calorific values measured with a combustion calorimeter varied from 17260 to 19767 J g-1. For the development of calibration models partial least square regression and cross validation was applied to correlate FTIR spectra determined with an attenuated total reflectance (ATR) unit to measured values of lignin or energy contents. The best models with high coefficients of determination (R2 (calibration) = 0.91 and 0.90; R2 (cross-validation) = 0.81 and 0.79) and low root mean square errors of cross validation (RMSECV = 0.77% and 62 J g-1) for lignin and energy determination, respectively, were obtained after data pre-processing and automatic wavenumber restriction. The calibration models were validated by analyses of independent sets of wood samples yielding R2 = 0.88 and 0.86 for lignin and energy contents, respectively.ConclusionsThese results show that FTIR-ATR spectroscopy is suitable as a high-throughput method for lignin and energy estimations in large data sets. Our study revealed that the intra-specific variations in lignin and energy contents were unrelated to each other and that the lignin content, therefore, was no predictor of the energy content. Employing principle component analyses we showed that factor loadings for the energy content were mainly associated with carbohydrate ring vibrations, whereas those for lignin were mainly related to aromatic compounds. Therefore, our analysis suggests that it may be possible to optimize the energy content of trees without concomitant increase in lignin.

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Novel 2‐Substituted Quinolin‐4‐yl‐benzenesulfonate Derivatives: Synthesis, Antiproliferative Activity, and Inhibition of Cellular Tubulin Polymerization

Cited by 13 publications

References 43 publications

Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells

Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells

Derivatives of 6-cinnamamido-quinoline-4-carboxamide impair lysosome function and induce apoptosis

FTIR-ATR-based prediction and modelling of lignin and energy contents reveals independent intra-specific variation of these traits in bioenergy poplars

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