Paclitaxel anticancer activity is enhanced by the MEK 1/2 inhibitor PD98059 in vitro and by PD98059-loaded nanoparticles in BRAFV600E melanoma-bearing mice

Mekkawy, Aml I; Naguib, Youssef W.; Alhaj‐Suliman, Suhaila O.; Wafa, Emad I.; Ebeid, Kareem; Acri, Timothy M.; Salem, Aliasger K.

doi:10.1016/j.ijpharm.2021.120876

Cited by 12 publications

(7 citation statements)

References 46 publications

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“…Previous studies have found that MEK inhibitor can truly induce G1 cell cycle arrest in tumor cells. The ERK pathway is constitutively activated, which indicated that the ERK pathway might be a potential therapeutic target ( 47 , 48 ). Moreover, there is an interesting observation that cell cycle arrest was induced at the G2/M phase by PTX alone and at the G0/G1 phase by PTX/NPs as well.…”

Section: Discussionmentioning

confidence: 99%

A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma

Xie

Hua

et al. 2022

Front. Oncol.

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Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.

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Section: Discussionmentioning

confidence: 99%

A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma

Xie

Hua

et al. 2022

Front. Oncol.

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“…The plates were then incubated at 37 °C. After 2 h, the absorbance was measured at 490 nm using a Spectra Max plus 384 Microplate reader (Molecular Devices, Sunnyvale, CA, USA) 74 . Also, before adding the MTS reagents, cells were examined under a cell imaging system (EVOS FL Digital Microscope using a 20x objective lens, total magnification = 200×).…”

Section: Methodsmentioning

confidence: 99%

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Mohammed

El-Hafeez

Ebeid

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC 50 s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC 50 values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC 50 values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC 50 = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.

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“…PMG5 were further characterized by assessing the average hydrodynamic diameter, PDI, and net surface charge (zeta potential) using a Zetasizer Nano ZS (Malvern Panalytical, Malvern, UK) as previously described ( 62 ). In addition, the shape and surface morphology of PMG5 were further examined using a Hitachi SEM (Hitachi High-Technologies, Schaumburg, IL) ( 63 ). PLGA, PAMAM, and PMG5 were also characterized for heat flow properties by analyzing the thermograms obtained from the differential scanning calorimeter (DSC Q20, TA Instruments, New Castle, DE) equipped with a refrigerated cooling system (RCS90) (TA Instruments, New Castle, DE), as previously described ( 64 ).…”

Section: Methodsmentioning

confidence: 99%

“…Plates were then incubated at 37°C with 5% CO 2 for 48 hours. Next, Cell Titer 96 aqueous MTS reagent [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, purchased from Promega Corporation, San Luis Obispo, CA] was added to the cells following the manufacturer's instructions (63,(68)(69)(70). After incubation for 2 hours, cell viability (%) was calculated on the basis of the absorbance measured at 490 nm using a SpectraMax Plus spectrophotometer (Molecular Devices, San Jose, CA).…”

Section: Cytotoxicity Studymentioning

confidence: 99%

Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

et al. 2022

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In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. Here, we have synthesized a previously unexplored cationic polymeric nanoparticle formulation using polyamidoamine dendrimers and poly( d , l -lactic- co -glycolic acid) that demonstrate adjuvant properties in vivo. Tumor-challenged mice vaccinated with an adenovirus-based cancer vaccine [encoding tumor-associated antigen (TAA)] and subsequently treated with this nanoparticulate formulation showed significant increases in TAA-specific T cells in the peripheral blood, reduced tumor burden, protection against tumor rechallenge, and a significant increase in median survival. An investigation into cell-based pathways suggests that administration of the nanoformulation at the site of the developing tumor may have created an inflammatory environment that attracted activated TAA-specific CD8 + T cells to the vicinity of the tumor, thus enhancing the efficacy of the vaccine.

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Paclitaxel anticancer activity is enhanced by the MEK 1/2 inhibitor PD98059 in vitro and by PD98059-loaded nanoparticles in BRAFV600E melanoma-bearing mice

Cited by 12 publications

References 46 publications

A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma

A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

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