Survival Rate Of Cancer Cells Research Articles

Preparation and characterization of sodium alginate/phosphate-stabilized amorphous calcium carbonate nanocarriers and their application in the release of curcumin

Phosphate-stabilized amorphous calcium carbonate (ACCP) has excellent biocompatibility, bioactivity, and biodegradability, and can be easily synthesized and stored. However, unmodified ACCP, as a controlled drug release carrier, decomposes rapidly in an acidic environment and highly depends on the system’s pH value, which can not meet the need for long-term release of active substances, thus limiting its application scope. To realize the specific pH responsiveness of ACCP nanoparticles, we designed and synthesized monodisperse sodium alginate/ACCP (Alginate/ACCP) composite nanoparticles in this paper. After ultrasonic treatment, nanoparticles with an average particle size less than 200 nm could form stable water dispersion that could be dispersed for up to 10 d. Based on the specific pH sensitivity of sodium alginate, the drug-controlled release performance of composite nanoparticles and the therapeutic effect of drug-loaded nanoparticles on A549 cancer cells were studied. The results indicated that under the same pH condition, the curcumin (Cur) release rate of composite nanoparticles gradually decreased with sodium alginate addition. When the dosage of sodium alginate was 1.0 mg ml−1, the cumulative drug release rate of nanoparticles in 40 h was only about 35%. Besides, the drug-loaded nanoparticles showed the excellent killing ability of cancer cells, and the survival rate of cancer cells decreased in a concentration-dependent manner. Therefore, through reasonable optimization design, we can synthesize composite nanoparticles with excellent sustained-release properties to provide a new strategy for cancer cells’ long-term treatment.

Изучение физико-химических свойств и биологической активности экстрактов из высушенной биомассы каллусных, суспензионных клеток и корневых культур in vitro

Introduction. One of the urgent problems of medicine and biology is the use of plant objects as industrial producers of target metabolites in vitro. In vitro cells can be used as pharmaceutical preparations. Study objects and methods. The present research featured medicinal plants that grow in the Siberian Federal district and are a popular source of medicinal raw materials. The physicochemical properties, e.g. total ash content in extracts, the content of heavy metals, the content of organic solvents in the extracts, and the mass loss upon drying was determined by standard methods. The antimicrobial properties of in vitro extracts were determined by the diffusion method and the method based on optical density measurement. The list of opportunistic and pathogenic test strains included the following microorganisms: E. coli ATCC 25922, S. aureus ATCC 25923, P. vulgaris ATCC 63, P. aeruginosa ATCC 9027, and C. albicans EMTC 34. The number of viable cancer cells was determined using the MTT colorimetric method. Results and discussion. The paper describes the physicochemical properties, safety indicators, antioxidant activity, antimicrobial activity, and antitumor properties of extracts of a complex of biologically active substances obtained in vitro from the dried biomass of callus and suspension cell cultures and root cultures. The root extracts proved to have the maximum antimicrobial and cytotoxic properties. They could reduce the survival rate of cancer cells to 24.8–36.8 %. Conclusion. The research featured extracts obtained from the dried biomass of callus and suspension cell cultures and root cultures in vitro of safflower leuzea (Leuzea carthamoides L.), Rhodiola rosea (Rhodiola rosea L.), various sorts of skullcap (Scutellaria baicalensis L., Scutellaria andrachnoides L., Scutellaria galericulata L.), Potentilla alba (Potentilla alba L.) and ginseng (Panax L.). The results showed that the extracts can be used for the production of pharmaceuticals and biologically active additives with antitumor, antimicrobial, and antioxidant properties.

Stem Cells in Tumour Microenvironment Aid in Prolonged Survival Rate of Cancer Cells and Developed Drug Resistance: Major Challenge in Osteosarcoma Treatment.

Osteosarcoma is an aggressive bone cancer found in children and adolescents. The combined treatment strategy includes the surgical removal of tumour and subsequent chemotherapy to prevent the reoccurrence has been a widely accepted approach. However, the drug resistance developed by tumour cells causes recurrence of cancer. It is imperative to understand the molecular mechanism involved in the development of drug resistance and tumour progression for developing potential therapy. Tumour microenvironment and cellular cross-talk via activation of various signalling pathways are responsible for tumour progression and metastasis. The comprehensive reviews are already available on the tumour microenvironment, signalling cascades responsible for tumour progression, and cellular crosstalk between malignant cells and immune cells. Therefore, we intend to provide comprehend review postulating the importance of mesenchymal stem cells (MSCs) in osteosarcoma progression and metastasis. This paper is aimed to provide information sequentially includes: tumour microenvironment, MSCs role in osteosarcoma progression, the hypoxic environment in MSCs recruitment at the tumour site and the importance of exosomes in tumorigenesis, progression and metastasis. Overall, this review may enlighten the research on the role of MSCs and MSCs derived exosome in osteosarcoma progression and drug resistance. This possibly may result in developing novel therapeutic approaches to combat the osteosarcoma effectively and contributes for the development of prognosis tools for early diagnosis.

Drug-loaded copper sulfide nanoparticles with high photothermal conversion and pH-stimuli response for drug delivery

In recent years, the incidence of malignant tumors is increasing year by year. Therefore, new antitumor drugs and treatment modalities are urgently needed. While, the biggest challenge to oncology drugs is to treat tumors in a safe and effective manner. Currently, most of the cancer patients in treatment are suffering due to side effects of oncology drugs. In order to reduce negative effects of tumor drugs, formulations of multifunctional nanocarriers have attracted attention because of their significant biological activity without damage to normal cells. These include formulations such as drug-loaded silica nanoparticles, photothermal treatment of gold nanoparticles, photodynamic therapy of copper sulfide nanoparticles and other multifunctional nanocomposites. In this study, a novel kind of high photothermal conversion CuS NPs as a pH-sensitive drug release system is going to be introduced. Firstly, CuS NPs with a uniform particle size was prepared by copper ions and sulfur ions in solution. Secondly, the PDA was modified on the surface of CuS NPs and DOX was adsorbed on the outside of PDA via non-covalent self-assembly. Finally, a drug-loaded core-shell nanoparticle DOX@CuS/PDA was obtained, with the core of CuS NPs and the shell of PDA. Further studies on DOX@CuS/PDA were performed to verify its anti-cancer effect. Surface morphology of DOX@CuS/PDA was observed by transport electronic microscope (TEM). TEM images show that DOX@CuS/PDA is uniform with a size of 70± 10 nm and appears as a spherical shape with a CuS NPs core. After comprehensive consideration of absorbance test, wavelength penetration capability and equipment, 808 nm near-infrared light was considered to be the most suitable light source. The 200 μg/mL of CuS NPs solution was heated to 54°C in 120 s under the irradiation of 808 nm near-infrared light with a power of 1 W/cm2, and the photothermal conversion rate was as high as 34.2%. The temperature of DOX@CuS/PDA was raised to 41.4°C in the same condition. In vitro release assay, the cumulative release of DOX at 72 h in the environment of pH 5.0 was 6 times higher than that of pH 7.4, which proves that DOX@CuS/PDA possesses a significant pH-stimulation response mechanism. Interestingly, DOX is adsorbed on the surface of the PDA through non-covalent self-assembly. When DOX@CuS/PDA stimulated by weak acid environment, this state of non-covalent self-assembly is undermined and the DOX is released. The mechanism of drug loading and pH response release was introduced in details. In the cancer cell experiments of DOX@CuS/PDA in vitro , the survival rate of cancer cells is 27%−33%, which effectively enhances the killing effect of tumor cells. It shows that the combination of advertising heat therapy and chemotherapy has good synergy, through the calculation of coordination coefficient. CuS NPs converts light energy into heat energy under 808 nm near-infrared lights to kill tumor cells by thermal effect and the DOX in DOX@CuS/PDA will accelerate release in a weak acid environment of tumor site. Tumor cells can be effectively killed by combining photothermal therapy with drug therapy. From the above, a novel research is put forward in this study for the combination of photothermal therapy and chemotherapy and provides a new understanding of drug-loaded by adsorption and pH-stimuli response.

Moringa peregrina Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

Moringa grows in the tropical and subtropical regions of the world. The genus Moringa belongs to family Moringaceae. It is found to possess various medicinal uses including hypoglycemic, analgesic, anti-inflammatory, hypolipidemic, and antioxidant activities. In this study, we investigated the antimicrobial and the anticancer activity of the Moringa peregrina as well as Moringa oleifera leaves extracts grown locally in Egypt. Results indicated that most of the extracts were found to possess high antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and fungus. The survival rate of cancer cells was decreased in both hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines when treated with Moringa leaves extracts. In addition, the cell cycle progression, apoptosis, and cancer-related genes confirmed its anticancer effect. The toxicity of each extract was also tested using the normal melanocytes cell line HFB4. The toxicity was low in both Moringa peregrina and Moringa oleifera leaves extracts. Furthermore, GC/MS analysis fractionized the phytochemicals content for each potential extract. In conclusion, results suggested that the Moringa peregrina and Moringa oleifera leaves extracts possess antimicrobial and anticancer properties which could be attributed to the bioactive phytochemical compounds present inside the extracts from this plant. These findings can be used to develop new drugs, especially for liver cancer chemotherapy.

Delaying Anticancer Drug Delivery by Self-Assembly and Branching Effects of Minimalist Dendron-Drug Conjugates.

Self-assembly of a covalently-bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach with a small PEG-dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) studies indicate the formation of stable, low-disperse nanoparticles at 10-5 m in H2 0, which could also be responsible for the biological effects. An ultrasensitive LC-MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.

Collagen type I induces EGFR-TKI resistance in EGFR-mutated cancer cells by mTOR activation through Akt-independent pathway.

Primary resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) is a serious problem in lung adenocarcinoma patients harboring EGFR mutations. The aim of this study was to examine whether and how collagen type I (Col I), the most abundantly deposited matrix in tumor stroma, affects EGFR‐TKI sensitivity in EGFR‐mutant cells. We evaluated the EGFR‐TKI sensitivity of EGFR‐mutated cancer cells cultured with Col I. Changes in the activation of downstream signaling molecules of EGFR were analyzed. We also examined the association between the Col I expression in tumor stroma in surgical specimens and EGFR‐TKI response of postoperative recurrence patients with EGFR mutations. Compared to cancer cells without Col I, the survival rate of cancer cells cultured with Col I was significantly higher after EGFR‐TKI treatment. In cancer cells cultured with and without Col I, EGFR‐TKI suppressed the levels of phosphorylated (p‐)EGFR, p‐ERK1/2, and p‐Akt. When compared to cancer cells without Col I, expression of p‐P70S6K, a hallmark of mTOR activation, was dramatically upregulated in cancer cells with Col I. This activation was maintained even after EGFR‐TKI treatment. Simultaneous treatment with EGFR‐TKI and mTOR inhibitor abrogated Col I‐induced resistance to EGFR‐TKI. Patients with Col I‐rich stroma had a significantly shorter progression‐free survival time after EGFR‐TKI therapy (238 days vs 404 days; P < .05). Collagen type I induces mTOR activation through an Akt‐independent pathway, which results in EGFR‐TKI resistance. Combination therapy using EGFR‐TKI and mTOR inhibitor could be a possible strategy to combat this resistance.

Anti-cancer effects of Staphylococcal Enterotoxin type B on U266 cells co-cultured with Mesenchymal Stem Cells

BackgroundMalignant plasma cells are responsible for Multiple Myeloma (MM). Myeloma Cells (MCs) are located in Bone Marrow (BM) and are in contact with stromal cells. The BM-derived Mesenchymal Stem Cells (BM-MSCs) affect MCs biology through different mechanisms. Currently, Staphylococcal Enterotoxin B (SEB) has been introduced as an anti-tumor agent that is able to kill cancer cells. The present study examined the effects of SEB on MCs and MSCs as an anti-tumor substance. MethodsU266 cells co-cultured on BM-MSCs and treated with SEB and cell viability was analyzed by MTT assay and flow cytometry. The expression levels of IKKb, IL-6, IL-10, and TGF-β genes were evaluated by Real Time-PCR technique in U266 cells and BM-MSCs. ResultsData showed that in the presence of SEB, BM-MSCs support U266 cells proliferation and survival. Moreover, SEB, BM-MSCs and BM-MSCs Conditioned Medium (CM) up-regulated IL-6 and IL-10 expression in U266 cells. Additionally, U266 cells showed increased levels in IKKb expression in presence of SEB or BM-MSCs, while expression of IKKb in U266 cells was down-regulated in coexistence of SEB with BM-MSCs or SEB with CM. Also, TGF-β remained without any changes. DiscussionAll in all, SEB can be an appropriate candidate to decrease proliferation and survival rate of cancer cells and it can make noticeable alteration in expression of some genes in U266 cells and BM-MSCs. Further molecular studies are needed to identify the mechanism of action of SEB on U266 cells and BM-MSCs.

Apoptosis induction effect of siRNA recombinant expression vector targeting Livin and Survivin gene simultaneously on human colon cancer cells

To investigate the effect of siRNA targeting Livin and Survivin gene simultaneously on the proliferation and apoptosis of human colon cancer cells. SiRNA recombinant expression vectors targeting Livin and Survivin gene simultaneously were constructed and transfected into human colon cancer cell line Lovo. The effects of siRNA recombinant expression vector on Lovo cells were detected by RT-PCR, Western blot, MTT reduction assay and flow cytometry. It was confirmed by restriction endonuclease and sequence analysis that siRNA recombinant expression vector targeting Livin and Survivin gene simultaneously was constructed successfully. The suppressive rates of siRNA targeting Livin and Survivin gene simultaneously on Livin mRNA and protein expression were 27.9% and 22.3% respectively, and those on Survivin mRNA and protein expression were 32.2% and 40.9% respectively. The survival rate of cancer cells was decreased whereas the apoptotic rate was increased, but the coordinate repression was weaker than Livin and Survivin RNA interference alone. siRNA targeting Livin and Survivin gene simultaneously can decrease the expression of Livin and Survivin gene, suppress cell proliferation and induce cell apoptosis in human colon cancer. The coordinate repression was weaker than Livin and Survivin RNA interference alone.

Localised heating of tumours utilising injectable magnetic nanoparticles for hyperthermia cancer therapy

This study reports an investigation of hyperthermia cancer therapy utilising an alternating magnetic field to induce a localised temperature increase on tumours by using injectable magnetic nanoparticles. In-vitro and in-vivo experiments represent the feasibility of hyperthermia cancer therapy. A feedback temperature control system was first developed to keep the nanoparticles at a constant temperature to prevent overheating in the tumours such that a safer and more precise cancer therapy becomes feasible. By using the feedback temperature control system, magnetic nanoparticles can be heated up to the specific constant temperatures, 37, 40, 42, 45, 46 and 47 degrees C, respectively, with a variation less than 0.2 degrees C. With this approach, the in-vitro survival rate of tumour cells at different temperatures can be systematically explored. It was experimentally found that the survival rate of cancer cells can be greatly reduced while CT-26 cancer cells were heated above 45 degrees C. Besides, localised temperatures increase as high as 59.5 degrees C can be successfully generated in rat livers by using the proposed method. Finally, complete regression of tumour was achieved. The developed method used injectable magnetic nanoparticles and may provide a promising approach for hyperthermia cancer therapy.

高温ハイパーサーミア用複合発熱体に関する一考察

Hyperthermia is a therapeutic technique against cancer. It necrotizes cancer cells by applying heat at about 43°C, at which the survival rate of cancer cells drastically drops. However, in case of a substantially large tumor, there is a possibility that cancer cells may survive when there is a difference in the temperature between the central part and marginal region. For this condition, high-temperature hyperthermia is proposed as a way to ensure that the malignant tumor is necrotized. In this study, using the soft heating method, which is a kind of inductive heating method, with hybrid heaters, we examined the temperature distributions of hybrid heaters that varies with the configuration of metal rings for the thermosensitive magnetic material.