<i>In Vitro</i> Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs

Iijima, Yosuke; Bandow, Kenjiro; Sano, Miho; Hino, Shunsuke; Kaneko, Takahiro; Horie, Norio; Sakagami, Hiroshi

doi:10.21873/anticanres.13882

Cited by 22 publications

(35 citation statements)

References 18 publications

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“…Three popular anticancer drugs, 5-FU, abraxane and cisplatin, dosedependently reduced the viable cell number of HSC-2 cells (black circle, Exp. I and II, Figure 7), confirming our previous finding (15). We next investigated the combination effect of these anticancer drugs and Chi-NP (0.08~1.25 mg/ml).…”

Section: Figure 5 Effect Of Chitosan Magnetic Nanoparticles On the Gsupporting

confidence: 89%

“…To achieve complete cell attachment, cells were inoculated at 2×10 3 cells/well in a 96-microwell plate and cultured for 48 h, unless otherwise stated. Attached cells were incubated for a further 48 h in fresh medium containing various concentrations of the test samples to determine the relative viable cell number in triplicate by the MTT method, as described previously (15).…”

Section: Characterization Of Chitosan Samples and Chi-npmentioning

confidence: 99%

“…Cells (approximately 10 6 cells) grown in 100 mm dishes were harvested by trypsinization, fixed, treated with ribonuclease A, stained with propidium iodide, filtered through cell strainer to remove the aggregated cells and debris and then subjected to cell-cycle analysis with Cell Sorter Software version 2.1.2. (SONY Imaging Products and Solution Inc., Tokyo, Japan), as described previously (15).…”

Section: Characterization Of Chitosan Samples and Chi-npmentioning

confidence: 99%

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Biological Properties of the Aggregated Form of Chitosan Magnetic Nanoparticle

Paulino-Gonzalez¹,

Sakagami²,

Bandow³

et al. 2020

In Vivo

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Background/Aim: Chitosan-coated iron oxide nanoparticles (Chi-NP) have gained attention because of their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. In this study, we investigated various biological properties of Chi-NP. Materials and Methods: Chi-NP was prepared by mixing magnetic NP with chitosan FL-80. Particle size was determined by scanning and transmission electron microscopes, cell viability by MTT assay, cell cycle distribution by cell sorter, synergism with anticancer drugs by combination index, PGE 2 production in human gingival fibroblast was assayed by ELISA. Results: The synthetic process of Chi-NP from FL-80 and magnetic NP increased the affinity to cells, up to the level attained by nanofibers. Upon contact with the culture medium, Chi-NP instantly formed aggregates and interfered with intracellular uptake. Aggregated Chi-NP did not show cytotoxicity, synergism with anticancer drugs, induce apoptosis (accumulation of subG1 cell population), protect the cells from X-ray-induced damage, nor affected both basal and IL-1β-induced PGE 2 production. Conclusion: Chi-NP is biologically inert and shows high affinity to cells, further confirming its superiority as a scaffold for drug delivery.

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Section: Figure 5 Effect Of Chitosan Magnetic Nanoparticles On the Gsupporting

confidence: 89%

Section: Characterization Of Chitosan Samples and Chi-npmentioning

confidence: 99%

Section: Characterization Of Chitosan Samples and Chi-npmentioning

confidence: 99%

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Biological Properties of the Aggregated Form of Chitosan Magnetic Nanoparticle

Paulino-Gonzalez¹,

Sakagami²,

Bandow³

et al. 2020

In Vivo

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“…We have recently reported that several G 2 /M blockers such as taxanes paclitaxel [Taxol ® , the first microtubule stabilizing agent (24)] and docetaxel (25), and 3-styrylchromone derivatives [7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1benzopyran-4-one, 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7methoxy-4H-1-benzopyran-4-one] show very high TS values (>7267, >86122, 301 and 182, respectively) (26). However, many reports, including ours, demonstrated that microtubuletargeted agents have potent neurotoxicity, adversely affecting the quality of life of patients on a long-term basis (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

et al. 2020

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Aim: The aim of this study was to investigate the antitumor potential of guaiazulene-3-carboxylate derivatives against oral malignant cells. Materials and Methods: Twelve guaiazulene-3-carboxylate derivatives were synthesized by introduction of either with alkyl group [1-5], alkoxy group [6, 7], hydroxyl group [8, 9] or primary amine [10-12] at the end of sidechains. Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC 50) against 3 human oral mesenchymal cell lines to that against 4 human oral squamous cell carcinoma (OSCC) cell lines. Potencyselectivity expression (PSE) was calculated by dividing TS value by CC 50 value against OSCC cell lines. Cell cycle analysis was performed by cell sorter. Results: [6, 7] showed the highest TS and PSE values, and induced the accumulation of both subG 1 and G 2 /M cell populations in HSC-2 OSCC cells. Quantitative structure-activity relationship analysis demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the 3D shape, electric state and ionization potential. Conclusion: Alkoxyl guaiazulene-3carboxylates [6, 7] can be potential candidates of lead compound for developing novel anticancer drugs.

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“…PC12, a rat pheochromocytoma cell line derived from adrenal medulla; SH-SY5Y, a human neuroblastoma cell line cloned from a human bone marrow biopsy-derived line called SK-N-SH; human myeloblastic leukemia (ML-1); and human oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingival tissue), and HSC-2, HSC-3, and HSC-4 (derived from tongue)] were purchased from Riken Cell Bank (Tsukuba, Japan). PC12, SH-SY5Y (15), Ca9-22, HSC-2, HSC-3 and HSC-4 cells (14) were grown at 37˚C in DMEM supplemented with 10% heat-inactivated FBS, 100 units/ml, penicillin G and 100 μg/ml streptomycin under a humidified atmosphere with 5% CO 2 , while ML-1 cells were cultured in RPMI-1640 supplemented with 10% FBS and antibiotics (16). These cell lines were used for the comparison of X-ray sensitivity.…”

Section: Methodsmentioning

confidence: 99%

Augmentation of Neurotoxicity of Anticancer Drugs by X-Ray Irradiation

Nakaya

Sakagami

Koga‐Ogawa

et al. 2020

In Vivo

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Background: In order to investigate the combination effect of anticancer drugs and X-ray irradiation on neurotoxic side-effects (neurotoxicity), a method that provides homogeneously X-ray-irradiated cells was newly established. Materials and Methods: PC12 cell suspension was irradiated by X-ray (0.5 Gy) in serum-supplemented medium, immediately inoculated into 96-microwell plates and incubated overnight. The medium was replaced with fresh serum-depleted medium containing 50 ng/ml nerve growth factor to induce differentiation toward nerve-like cells with characteristic neurites according to the overlay method without changing the medium. The differentiated cells were treated by anticancer drugs as well as antioxidants, oxaliplatin or bortezomib, and the viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide method. Results: Antioxidants and anticancer drugs were cytotoxic to differentiating PC12 cells. Combination of anticancer drugs and X-ray irradiation slightly reduced cell viability. Conclusion: The present 'population irradiation method' may be useful for the investigation of the combination effect of X-ray irradiation and any pharmaceutical drug. X-Rays are used for many purposes in various fields. This includes the visualization of the distribution and therapeutic effects of drugs by X-ray computed tomography (1); the assessment of chemical element changes by energy dispersive X-ray spectrometry (2); the analysis of crystal structure by Xray diffraction (3); the analysis of oral mucosal distribution of trace metal elements by X-ray fluorescence with synchrotron radiation and particle-induced X-ray emission, and the estimation of chemical states of elements by X-ray absorption fine-structure analysis (4); the visual inspection of passenger baggage in airports by X-ray images (5); and therapeutic applications in medicine (6). Radiation, such as X-rays, and drugs, are reported to exert dose-dependent biphasic effects (7). X-Ray irradiation has been reported to stimulate the production of reactive oxygen-species such as superoxide and nitrite (8, 9), the secretion of Fas ligand (10), the accumulation of cells in the G 2 +M phase in the cell cycle (11), and the shortening of telomeres (12). On the other hand, at lower doses of X-irradiation, beneficial effects (known as hormesis) can be induced. For example, Xirradiation at 10 mGy (but not 50 or 100 mGy) reduced the frequency of micronucleated cells in human lymphocytes to below the spontaneous level (13). Recently, we discovered that among anticancer drugs, platinum preparations (cisplatin, carboplatin, oxaliplatin) and proteasome inhibitor bortezomib showed potent cytotoxicity not only against normal oral keratinocytes (14) but also against PC12 nerve-like cells (Iijima et al., unpublished data). The neurotoxicity of anticancer agents and X-ray irradiation is a recent research topic in today's aging society. In the present study, we investigated whether cytotoxic doses of X-ray irradiation further augment neurotoxicity...

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In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs

Cited by 22 publications

References 18 publications

Biological Properties of the Aggregated Form of Chitosan Magnetic Nanoparticle

Biological Properties of the Aggregated Form of Chitosan Magnetic Nanoparticle

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

Augmentation of Neurotoxicity of Anticancer Drugs by X-Ray Irradiation

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