Active caspase-3 expression levels as bioindicator of individual radiosensitivity

Santos, Nilcilene Nascimento dos; Silva, Rafael F; Pinto, Maria Benegelânia; Silva, Edvane B Da; Tasat, Deborah Ruth; Amaral, Ademir

doi:10.1590/0001-3765201720160697

Cited by 19 publications

(9 citation statements)

References 57 publications

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“…f) which is critical in carrying out apoptosis. An increased level of caspase‐3 can serve a bio‐indicator of radiosensitivity . VCN‐2 in combination with radiation also resulted in an increase in the BECN‐1 mRNA levels (Fig.…”

Section: Discussionmentioning

confidence: 92%

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Baruah

Kma

2018

BioFactors

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Non‐small cell lung cancer (NSCLC) has a very high rate of incidence and is resistant to chemo‐ and radiotherapy. Vicenin‐2 (VCN‐2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective, anticancer, and radiosensitizing properties. We have conducted this study to check the effect of VCN‐2 on the cell viability and the effect on PTEN (Phosphatase and tensin homolog), PI3KCA (Phosphatidylinositol 4, 5‐biphosphate 3‐kinase catalytic subunit alpha isoform/PI3K 110α subunit), and Akt1 when VCN‐2 was used alone and in combination with radiation in the NSCLC cell line NCI‐H23 (H23). We have also checked the effect of VCN‐2 on various pro‐ and anti‐apoptotic genes and the ultra‐morphological changes that occurred in the cells when VCN‐2 is used alone and in combination with radiation. VCN‐2 was able to lower cancer cell survival and phosphorylated Akt while promoting the expression of pro‐apoptotic genes and down‐regulating anti‐apoptotic genes. We also observed the apoptosis‐associated ultra‐morphological changes in the VCN‐2‐treated cells. Our study have demonstrated that VCN‐2 can be a potential chemotherapeutic and radiosensitizing agent in NSCLC. © 2018 BioFactors, 45(2):200–210, 2019

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Section: Discussionmentioning

confidence: 92%

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Baruah

Kma

2018

BioFactors

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“…Among the 16 downregulated proteins, caspase 3 was the most downregulated in the RT-R-MDA-MB-231 cells, which is suggested as one of the mechanisms for RT resistance [ 20 ]. Figure 1 A shows a graphical representation of the proteins concerning the fold change.…”

Section: Resultsmentioning

confidence: 99%

Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells

Paramanantham

Jung

et al. 2021

IJMS

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Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (β-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.

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“…caspase‐3 is a significant protease in the cascade reaction, and is therefore known as the 'hallmark enzyme' of cell apoptosis . Considering the importance of active caspase‐3 in the proteolytic cascade that ensures radiation‐induced apoptosis execution . To investigate the possible role of radiation‐induced heart disease, we examined the cleaved caspase‐3 and cyclophilin A expression levels in the heart of irradiated rats and found that, 6 Gy gamma irradiation induces a marked elevation in the former parameters compared with the corresponding normal values.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin‐potentiating factor isolated from Leiurus quinquestriatus scorpion venom alleviates cardiomyopathy in irradiated rats via remodelling of the RAAS pathway

Hasan

Radwan

Galal

2019

Clin Exp Pharma Physio

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The objective of this work was to evaluate the effect of a bradykinin‐potentiating factor (BPF) isolated from Leiurus quinquestriatus scorpion venom as a natural modulator of radiation‐induced cardiac damage. Four groups of rats were treated as follows; control group, group receiving BPF (1 µg/g b.wt i.p./biweekly) for 4 weeks, group irradiated at 6 Gy, group receiving BPF post‐irradiation for 4 weeks. Irradiation induced a significant elevation of myocardial parameters: atrial natriuretic peptide (ANP), cardiac troponin I (cTnI), potassium (K+) and creatine kinase (CK); vascular indices: lactate dehydrogenase (LDH), inducible nitric oxide synthase (iNOS) and endothelin I; oxidative stress indices: malondialdehyde (MDA) associated with a significant depletion of both reduced glutathione (GSH) in the cardiac tissue homogenate and serum ferric reducing antioxidant power (FRAP) depletion and significantly reinforced elevation of Renin Angiotensin Aldosterone System (RAAS) indices: serum angiotensin II (AngII) and aldosterone, and also protein expression of cleaved caspase‐3 and cyclophilin A. BPF administration altered the biochemical damage of radiation, specifically inhibited AngII formation, aldosterone release and prevented the histopathological and immunohistochemical alterations which were observed in cardiac tissue with significant reduction in mean arterial blood pressure (MAP) caused by irradiation. In conclusion, biochemical assays, histopathological and immunohistochemical findings of the present study demonstrated that exogenous BPF isolated from scorpion venom reduced the cardiomyopathy alterations induced by irradiation via remodelling of the RAAS pathway.

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Active caspase-3 expression levels as bioindicator of individual radiosensitivity

Cited by 19 publications

References 57 publications

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells

Bradykinin‐potentiating factor isolated from Leiurus quinquestriatus scorpion venom alleviates cardiomyopathy in irradiated rats via remodelling of the RAAS pathway

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