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Inhibition of Proliferation in U937 Cells Treated by Blue Light Irradiation and Combined Blue Light Irradiation/Drug.

ABSTRACT: The cell viability and apoptosis of tumor U937 cells treated by blue light (BL) irradiation have been examined. BL irradiation can specially inhibit the proliferation and promote the apoptosis of U937 cells, relating to the production of reactive oxygen species (ROS) and the decline of mitochondrial membrane potential (??m). The apoptosis is further associated with varying downregulated B-cell lymphoma-extra large (Bcl-XL) and B-cell lymphoma 2 (Bcl-2) genes, upregulated Bcl-2-associated X (Bax) gene, the activation of caspase-3 and caspase-9, and the cleavage of poly (ADP-ribose) polymerase (PARP) by the BL irradiation process. Moreover, BL irradiation induced proliferation inhibition is higher than that treated by a common chemotherapeutic drug of homoharringtonine (HHT). When we synergize BL irradiation with HHT (BL-HHT), a higher proliferation inhibition is obtained than that treated by BL irradiation or HHT alone. These results are helpful for establishing a low toxicity and high efficiency strategy of BL irradiation for clinical treatment of acute myeloid leukemia, not limited to U937 cells.

SUBMITTER: Zhuang J

PROVIDER: S-EPMC5983758 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Inhibition of Proliferation in U937 Cells Treated by Blue Light Irradiation and Combined Blue Light Irradiation/Drug.

Zhuang Jianjian J Liu Junsong J Gao Xuan X Li Hongdong H

International journal of molecular sciences 20180515 5

The cell viability and apoptosis of tumor U937 cells treated by blue light (BL) irradiation have been examined. BL irradiation can specially inhibit the proliferation and promote the apoptosis of U937 cells, relating to the production of reactive oxygen species (ROS) and the decline of mitochondrial membrane potential (ΔΨm). The apoptosis is further associated with varying downregulated B-cell lymphoma-extra large (Bcl-XL) and B-cell lymphoma 2 (Bcl-2) gene ...[more]

PMID: 29762467

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Project description:AimsAcute myeloblastic leukemia (AML) is the most common type of acute leukemia in adults. Despite numerous treatment strategies including chemotherapy and radiotherapy, a large number of patients do not respond to treatment and experience relapse. The main problem of these patients is the development of resistance to anti-cancer drugs. Therefore, any endeavor to reduce drug resistance in these patients is of high priority. In general, several mechanisms such as changes in drug metabolic pathways, drug inactivation, drug target alterations and reduced drug accumulation in the cells contribute to drug resistance of cancer cells. In this context, evidence suggests that exosomes could reduce drug resistance by removing drugs from their parent cells. In the present study, we aimed to investigate the effects of exosome release inhibition on the resistance of U937 cells to PEGylated liposomal doxorubicin (PLD).Main methodsIn order to find a suitable ABCG2 (ATP-binding cassette sub-family G member 2) transporter substrate, virtual screening was performed among a list of drugs used in leukemia and PLD was selected. U937 cells were treated with PLD with/without co-treatment with the exosome release inhibitor, GW4869. Released exosomes within different study groups were isolated and characterized to determine the differences between groups. Doxorubicin presence in the isolated exosomes was also measured by high performance liquid chromatography (HPLC) to confirm drug export through the exosomes. Finally, the effect of exosome inhibition on the cytotoxicity of PLD on U937 cells was determined using different cytotoxicity assays including the standard lactate dehydrogenase (LDH) release assay and the flow cytometric analysis of apoptotic and non-apoptotic cell death.Key findingsGW4869 treatment caused a significant decrease in the exosome release of U937 cells compared to the untreated cells, as evidenced by the reduction of the protein content of the isolated exosomes (P<0.05). Co-treatment with GW4869 significantly increased cytotoxic cell death in the groups treated with 0.5 and 1 µM PLD, compared to the same groups without GW4869 co-treatment (P<0.05). Interestingly, co-treatment with GW4896 and 0.5 µM PLD was enough to induce the same cytotoxic effect as that of the sole 1 µM PLD group.SignificanceOur findings showed that U937 cells increase their resistance against the cytotoxic effects of PLD through the exosome-mediated expelling of the drug. Inhibition of exosome release could prevent PLD efflux and consequently increase the vulnerability of the U937 cells to the cytotoxic effects of PLD. Our results along with prior studies indicate that the integration of exosome release inhibitors into the common PLD-containing chemotherapy regimens could significantly lower the required concentrations of the drug and consequently reduce its associated side effects. Further studies are warranted to identify clinically safe inhibitors and investigate their clinical efficacy.

Project description:BackgroundVisible light, in particular blue light, has been identified as an additional contributor to cutaneous photoageing. However, clinical studies demonstrating the clear effect of blue light on photoageing are still scarce, and so far, most studies have focused on broad-spectrum visible light. Although there is evidence for increased skin pigmentation, the underlying mechanisms of photoageing in vivo are still unclear. Furthermore, there is still a need for active ingredients to significantly protect against blue light-induced hyperpigmentation in vivo. Our study had two aims: to detect visible changes in skin pigmentation following repeated irradiation of the skin with LED-based blue light and to reduce pigmentation using suitable active ingredients.MethodWe conducted a randomized, double-blind and placebo-controlled clinical study on 33 female volunteers with skin phototypes III and IV. We used a repetitive blue light (4 × 60 J cm-2 , 450 nm) irradiation protocol on the volunteers' inner forearms. Using hyperspectral imaging, we assessed chromophore status. In addition, we took chromameter measurements and photographs to assess visible hyperpigmentation.ResultsWe measured significant changes in chromophore status (P < 0.001 vs baseline), that is of melanin, haemoglobin and oxygen saturation, immediately after blue light irradiation. In addition, we found visible skin colour changes which were expressed by a significant decrease in ITA° values (delta ITA° = -16.89, P < 0.001 vs baseline for the placebo group) and an increase in a* (delta a* = +3.37, P < 0.001 vs baseline for the placebo group) 24 h post-irradiation. Hyperpigmentation and skin reddening were mitigated by both a formulation containing 3% of a microalgal product and a formulation containing 3% niacinamide.ConclusionOur study sets out an efficient and robust protocol for investigating both blue light-induced cutaneous alterations, such as changes in skin chromophores, and signs of photoageing, such as hyperpigmentation. Moreover, we have shown evidence that both an extract of the microalga Scenedesmus rubescens and niacinamide (vitamin B3) have the potential to protect against blue light-induced hyperpigmentation.

Dataset Information

Inhibition of Proliferation in U937 Cells Treated by Blue Light Irradiation and Combined Blue Light Irradiation/Drug.

Publications

Inhibition of Proliferation in U937 Cells Treated by Blue Light Irradiation and Combined Blue Light Irradiation/Drug.

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