Anticancer Effects of a New Aminosugar-conjugated Platinum Complex Agent Against Cisplatin-resistant Gastric Cancer

Hayashi, Noriyuki; Kataoka, Hiromi; Yano, Shigenobu; Kikuchi, Jun‐ichi; Tanaka, Mamoru; Nishie, Hirotada; Kinoshita, Yuma; Miki, Hatano; Nomoto, Akihiro; Inoue, Masahiro; Mizoshita, Tsutomu; Shimura, Takaya; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Joh, Takashi

doi:10.21873/anticanres.11189

Cited by 10 publications

(7 citation statements)

References 15 publications

(16 reference statements)

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“…Drug resistance decreases the effectiveness of agents against cancer. Treatment methods such as chemotherapy have been adopted to combat drug resistance . Although achievements have been made, many cancers still develop MDR, which weakens the power of drugs in cancer therapy .…”

Section: Discussionmentioning

confidence: 99%

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

Zou

Zong

et al. 2017

J Cellular Molecular Medi

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MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR‐495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR‐495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol‐doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre‐treatment with miR‐495 before chemotherapy could improve the curative effect on MDR1‐based MDR cancer.

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Section: Discussionmentioning

confidence: 99%

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

Zou

Zong

et al. 2017

J Cellular Molecular Medi

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“…73,74 Therefore, γ-H 2 AX is one of the most sensitive markers of DSB formation induced by ionizing radiation. 75,76 The formation of γ-H 2 AX foci was observed using CLSM after immunofluorescence staining with γ-H 2 AX antibody (Figure 4A). Quantitative analysis of the average fluorescence intensities of γ-H 2 AX foci at 0.5 and 2 h after X-ray radiation is summarized in Figure 4B,C, respectively.…”

Section: In Vitro Radio-sensitizing Effects Of Ngm Micellesmentioning

confidence: 99%

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor

Qian

Ding

et al. 2022

ACS Appl. Mater. Interfaces

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Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G 2 /M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.

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“…Many different kinds of compounds have been found to be active in restraining the reproduction of cancer cells, and some of them have been used in clinical treatments. Platinating agents, including cisplatin (CDDP), carboplatin (CBDCA), and oxaliplatin (L-OHP) have been widely used in the treatment of a wide spectrum of solid tumors (Abu-Surrah & Kettunen, 2006 ; Rabik & Dolan, 2007 ; Hayashi et al., 2016 ). To reduce side effects of chemotherapy in normal tissues, or decrease in the concentration of drug, the limited spectrum of activity and resistance caused by platinum compounds (Karasawa & Steyger, 2015 ), on the development of design and synthesis of new non-platinum compounds with potential cytotoxicity have focused in recent years (Yilmaz et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and toxicity assessment of Fe ₃ O ₄ NPs grafted by ∼ NH ₂ -Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation

et al. 2020

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Superparamagnetic iron oxide nanoparticles have been synthesized using chain length of (3-aminopropyl) triethoxysilane for cancer therapy. First, we have developed a layer by layer functionalized with grafting 2,4-toluene diisocyanate as a bi-functional covalent linker onto a nano-Fe 3 O 4 support. Then, they were characterized by Fourier transform infrared, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and VSM techniques. Finally, all nanoparticles with positive or negative surface charges were tested against K562 (myelogenous leukemia cancer) cell lines to demonstrate their therapeutic efficacy by MTT assay test. We found that the higher toxicity of Fe 3 O 4 @SiO 2 @APTS $ Schiff base-Cu(II) (IC 50 : 1000 lg/mL) is due to their stronger in situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. For first time, the molecular dynamic simulations of all compounds were carried out afterwards optimizing using MMþ, Semi-empirical (AM1) and Ab-initio (STO-3G), Forcite Gemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. The energy (eV), space group, lattice parameters (Å), unit cell parameters (Å), and electron density of the predicted structures were taken from the CASTEP module of Materials Studio. The docking methods were used to predict the DNA binding affinity, ribonucleotide reductase, and topoisomerase II.

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Anticancer Effects of a New Aminosugar-conjugated Platinum Complex Agent Against Cisplatin-resistant Gastric Cancer

Abstract: Abstract. Background

Cited by 10 publications

References 15 publications

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor

Synthesis and toxicity assessment of Fe ₃ O ₄ NPs grafted by ∼ NH ₂ -Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation

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Anticancer Effects of a New Aminosugar-conjugated Platinum Complex Agent Against Cisplatin-resistant Gastric Cancer

Abstract: Abstract. Background

Cited by 10 publications

References 15 publications

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor

Synthesis and toxicity assessment of Fe 3 O 4 NPs grafted by ∼ NH 2 -Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation

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About

Synthesis and toxicity assessment of Fe ₃ O ₄ NPs grafted by ∼ NH ₂ -Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation