Induction of cell cycle arrest by increasing GTP-RhoA levels via Taxol-induced microtubule polymerization in renal cell carcinoma

Ren, Yu; Wang, Xue; Lou, Zhongguan; Huang, Shuaishuai; Zhuang, Haihui; Wang, Yuduo; Weng, Guobin; Wang, Ping

doi:10.3892/mmr.2017.6543

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…Previous studies indicated that NCTD 24 and PTX 25 induced cell cycle arrest in multiple cancer cells. Moreover, this study next clarified whether NCTD combined with PTX induces cell cycle arrest.…”

Section: Resultsmentioning

confidence: 98%

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

Hui

Chen

et al. 2021

Environmental Toxicology

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Prostate cancer (PCa), an extremely common malignancy in males, is the most prevalent disease in several countries. Norcantharidin (NCTD) has antiproliferation, antimetastasis, apoptosis, and autophagy effects in various tumor cells. Nevertheless, the antitumor effect of NCTD combined with paclitaxel (PTX), a chemotherapeutic drug, in PCa remains unknown. The cell growth, proliferative rate, cell cycle distribution, and cell death were determined by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyltetrazolium bromide, colony formation assay, PI staining, and Annexin V/PI staining by flow cytomertry, whereas the mitochondrial membrane potential (MMP) and endoplasmic reticulum (ER) stress was evaluated using the MitoPotential assay and ER‐ID red assay. We also evaluated the protein and mRNA expression of SIRTs by Western blotting and qRTPCR assay. Overexpression effectivity was measured by DNA transfection assay. Our study showed that cell viability and proliferative PC3 and DU145 rates were effectively inhibited after NCTD‐PTX combination. We also found that NCTD‐PTX combination treatment significantly enhance G2/M phase arrest, induction of cell death and ER stress, loss of MMP, and ER‐ or apoptotic‐related protein expression. Furthermore, NCTD‐PTX combination treatment was significantly decreasing the protein and mRNA expression of SIRT7 in PCa cells. Combination therapy effectively reduced cell viability, ER stress‐mediated apoptosis and p‐eIF2α/ATF4/CHOP/cleaved‐PARP expression inhibition in SIRT7 overexpression of PCa cells. These results indicate that NCTD combined with PTX induces ER stress‐mediated apoptosis of PCa cells by regulating the SIRT7 expression axis. Moreover, combination therapy may become a potential therapeutic strategy against human PCa.

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Section: Resultsmentioning

confidence: 98%

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

Hui

Chen

et al. 2021

Environmental Toxicology

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“…We began with evaluating the drug efficacy and mechanism of action in vitro. Taxol binds to the mitotic spindle apparatus and disrupts chromosomal segregation, which leads to mitotic catastrophe and cell death 21 , 36 , 37 . In vitro fluorescent imaging showed the internalization of Taxol646 in PS5A1 tumor cells after 1-h co-incubation (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment

Cai

Xiong

et al. 2023

Nat Commun

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The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.

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“…To investigate the efficacy of optoBBTB for Taxol delivery in our GEMM, we first evaluated its efficacy and mechanism of action in vitro. Taxol is known to binding to the mitotic spindle apparatus, and disrupt chromosomal segregation which leads to mitotic catastrophe and cell death ( 28, 29 ). In vitro studies showed the internalization of Taxol Janelia Fluor 646 in PS5A1 glioma cells after 1-hour co-incubation.…”

Section: Resultsmentioning

confidence: 99%

Optical Modulation of Blood-Brain-Tumor Barrier Permeability Enhances Drug Delivery in Diverse Preclinical Glioblastoma Models

Cai

Xiong

et al. 2022

Preprint

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Glioblastoma multiforme (GBM) is the most prevalent malignant tumor in the central nervous system. It has diverse phenotypes, including diffuse single-cell infiltration in which the tumor cells co-opt the normal microvasculature, and the neovascularization of an expanding tumor mass. The blood-brain-tumor barrier (BBTB) is a significant obstacle to GBM treatment and restricts entry of most FDA-approved effective oncology drugs. Herein, we report that picosecond laser excitation of vascular-targeted plasmonic gold nanoparticles (AuNPs) can non-invasively and reversibly modulate the BBTB permeability (optoBBTB). OptoBBTB enhances the delivery of paclitaxel (Taxol) in two genetically engineered glioma models (GEMM) that span the spectrum of GBM phenotypes. OptoBBTB followed by Taxol delivery effectively suppresses tumor growth and prolongs the survival time of both GEMM. Moreover, our results raise the possibility that paclitaxel, which is amongst the most widely used oncology drugs because of its proven efficacy but has been abandoned for GBM following its failure to efficacy in early phase clinical trials due to poor blood-brain barrier (BBB) penetration, could now be reconsidered in combination with strategies to increase BBB permeability. In summary, optoBBTB is a novel and effective approach to increase the delivery of therapeutics with limited BBB permeability to treat neoplastic and non-neoplastic brain diseases.

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Induction of cell cycle arrest by increasing GTP-RhoA levels via Taxol-induced microtubule polymerization in renal cell carcinoma

Cited by 9 publications

References 27 publications

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment

Optical Modulation of Blood-Brain-Tumor Barrier Permeability Enhances Drug Delivery in Diverse Preclinical Glioblastoma Models

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