Doxorubicin Changes Bax /Bcl-xL Ratio, Caspase-8 and 9 in Breast Cancer Cells

Sharifi, Simin; Barar, Jaleh; Hejazi, Mohammad Saeid; Samadi, Nasser

doi:10.15171/apb.2015.049

Cited by 121 publications

(94 citation statements)

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“…In the group of doxorubicin administration decreased the percentage of expression of mutant p53 and Bcl-2. It is proved that doxorubicin can decrease the expression of Bcl-2 with path induces the release of cytochrome c from mitochondria to the cytoplasm, activation of Caspase 9 and may induce apoptosis 22 and can reduce the expression of mutant p53. 23 However Doxorubicin cause side effects such as changes in the use of cardiovascular, 24;25 hepatotoxicity, 26 as well as their toxic effects on normal tissues of the body.…”

Section: Discussionmentioning

confidence: 99%

Effects of Co-Chemotherapy Ethyl Acetate Fraction of Eurycoma Longifolia Jack Roots and Doxorubicin Against Apoptosis Through Expression P53 Mutant and BCL-2

Mulyati

Nurani

Widyarini

2017

JKKI

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Background: It was found mutations of p53 gene in Breast cancer. Mutant p53 protein caused a decrease in cell apoptosis mechanisms through increased expression of Bcl-2. Breast cancer therapy is commonly used chemotherapy using Doxorubicin. However, effectiveness of the use of this chemotherapeutic agent is limited due to the emergence of side effects and toxic to normal cells. Therefore, it is necessary to develop new drugs for combination of chemotherapy. Eurycoma longifolia Jack roots has the potential as co-chemotherapy of breast cancer and it is not toxic to normal cells. Method: Rats were divided into 5 groups. Each group consisted of four female white Sprague Dawley rats. Group 1 (Normal), group 2 (DMBA 20 mg/kgB.W), group 3 (DMBA +Doxorubicin 1.12 mg/kgB.W), group 4 (DMBA +fractions 100 mg/kgB.W), group 5 (DMBA+Doxorubicin +fractions). All the rats were sacrificed at weeks 16 and to be taken their breast tissue. Immunohistochemistry was performed using a mouse monoclonal antibody mutant (BioGenex) and Bcl-2 (BIOSS). Results: expression of mutant p53 percentage obtained for group I (9.35 ± 0.32)%, II (21.65 ± 1.60)%, III (10.72 ± 2.52)%, IV (11.63 ± 3.39)%, V (12.72 ± 3.44)%, While the percentage of Bcl-2 expression obtained for I (20.62 ± 10.09)%, II (52.83 ± 3.61)%, III (24.38 ± 3.54)%, IV (38.01 ± 6.25)%, V (27.99 ± 4.27)%. The data was statistically tested by Kruskal Wallis test (p< 0.005). Conclussion: Co-chemotherapy of E. longifolia Jack roots and Doxorubicin can stimulate apoptosis through decreased in the expression of mutant p53 protein and Bcl-2 in breast tissue of rats induced by DMBA.

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Section: Discussionmentioning

confidence: 99%

Effects of Co-Chemotherapy Ethyl Acetate Fraction of Eurycoma Longifolia Jack Roots and Doxorubicin Against Apoptosis Through Expression P53 Mutant and BCL-2

Mulyati

Nurani

Widyarini

2017

JKKI

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“…The purpose of malignant tumor treatment is to selectively trigger tumor cell death (Hanahan and Weinberg, 2000). Because malignant tumors constantly strive to prevent cell death and survive, the process often leads to apoptosis resistance and chemotherapy resistance (Sharifi et al, 2015). TRAIL is an important member of the tumor necrosis factor superfamily that can induce tumor cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Correlation between TRAIL and caspase-8 expression and their relationship with cell proliferation and apoptosis in human osteosarcoma

Xu¹,

Shang²,

Zhuang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Osteosarcoma is a common malignant bone tumor that mainly affects children and adolescents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily. Caspase-8 appears in the upstream of apoptosis signaling pathway among caspases. We investigated TRAIL and caspase-8 levels in osteosarcoma patients to determine their correlation with cell proliferation and apoptosis. Osteosarcoma and osteochondroma patients receiving surgery in our hospital were selected. TRAIL and caspase-8 expression levels in tissue were determined by immunohistochemistry, and protein levels in cells were evaluated by western blotting. Human osteosarcoma cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The osteosarcoma and osteochondroma cell cycles and apoptosis were investigated by flow cytometry. Correlation analysis was applied to TRAIL and caspase-8 levels during cell apoptosis. Positive TRAIL and caspase-8 expression rates in osteosarcoma tissue were significantly lower than in the controls (P < 0.05). TRAIL (0.114 ± 0.002) and caspase-8 (0.352 ± 0.124) levels in experimental cells were obviously lower than in the controls (P < 0.05). Osteosarcoma cells in the experimental group demonstrated higher proliferation and lower apoptosis at 24, 48, and 72 h (P < 0.05). The experimental cell number increased in the G1 stage and decreased in the S stage (P < 0.05). TRAIL and caspase-8 proteins showed positive correlation with apoptosis in osteosarcoma (P < 0.05). Human osteosarcoma presented reduced TRAIL and caspase-8 levels with enhanced cell proliferation and reduced apoptosis. TRAIL and caspase-8 expression levels were positively correlated with apoptosis in osteosarcoma.

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“…The interactions between both in the cytosol and on mitochondria determine the fate of the cell for death or survival (8). Gene and protein expression of Bax in breast cancer cells increase sensitivity to apoptotic stimuli and decreases tumor enlargement while, Bcl-xL is another anti-apoptotic protein that inhibits apoptosis and stimulates the progress of breast cancer (6,7,9). In cancer cells, it has been demonstrated that the Bax/Bcl-2 ratio is diminished favoring the survival of cells, but treatment with anticancer drugs increased Bax/Bcl-2 ratio producing cell apoptosis by the intrinsic pathway (6,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Apoptosis is a process of programmed cell death that occurs in response to environmental stimuli and normal growth and homeostasis, during development, embryogenesis, modification of normal tissues, and appropriate strategy for prevention and treatment of cancer (5,6). Bcl-2 protein family plays an important role in the survival or death of a cell and in recent years these proteins have been the target of many antitumor drugs (7).…”

Section: Introductionmentioning

confidence: 99%

“…Gene and protein expression of Bax in breast cancer cells increase sensitivity to apoptotic stimuli and decreases tumor enlargement while, Bcl-xL is another anti-apoptotic protein that inhibits apoptosis and stimulates the progress of breast cancer (6,7,9). In cancer cells, it has been demonstrated that the Bax/Bcl-2 ratio is diminished favoring the survival of cells, but treatment with anticancer drugs increased Bax/Bcl-2 ratio producing cell apoptosis by the intrinsic pathway (6,(10)(11)(12).Caspase activity has been related to the different pathways of apoptosis, caspase-8 and caspase-10 features of the extrinsic pathway, whereas caspase-9 of the intrinsic pathway. Caspase-8 and caspase-9 (among others) are initiators of apoptosis and their activation triggers the caspase-3 effector, therefore, their increase stimulate apoptosis (5,13,14).…”

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confidence: 99%

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Apoptotic effect of noscapine in breast cancer cell lines

Quisbert-Valenzuela

Calaf

2016

International Journal of Oncology

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Abstract. Cancer is a public health problem in the world and breast cancer is the most frequently cancer in women. Approximately 15% of the breast cancers are triple-negative. Apoptosis regulates normal growth, homeostasis, development, embryogenesis and appropriate strategy to treat cancer. Bax is a protein pro-apoptotic enhancer of apoptosis in contrast to Bcl-2 with antiapoptotic properties. Initiator caspase-9 and caspase-8 are features of intrinsic and extrinsic apoptosis pathway, respectively. NF-κB is a transcription factor known to be involved in the initiation and progression of breast cancer. Noscapine, an alkaloid derived from opium is used as antitussive and showed antitumor properties that induced apoptosis in cancer cell lines. The aim of the present study was to determine the apoptotic effect of noscapine in breast cancer cell lines compared to breast normal cell line. Three cell lines were used: i) a control breast cell line MCF-10F; ii) a luminallike adenocarcinoma triple-positive breast cell line MCF-7; iii) breast cancer triple-negative cell line MDA-MB-231. Our results showed that noscapine had lower toxicity in normal cells and was an effective anticancer agent that induced apoptosis in breast cancer cells because it increases Bax gene and protein expression in three cell lines, while decreases Bcl-xL gene expression, and Bcl-2 protein expression decreased in breast cancer cell lines. Therefore, Bax/Bcl-2 ratio increased in the three cell lines. This drug increased caspase-9 gene expression in breast cancer cell lines and caspase-8 gene expression increased in MCF-10F and MDA-MB-231. Furthermore, it increased cleavage of caspase-8, suggesting that noscapineinduced apoptosis is probably due to the involvement of extrinsic and intrinsic apoptosis pathways. Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced expression, probably due to decrease in NF-κB gene and protein expression and also by increase of IκBα gene expression induced by this drug. IntroductionCancer is a leading cause of death in both more and less economically developed countries; the burden is expected to grow worldwide due to the growth and aging of the population and improvements in early detection and treatment (1). Cancer is a major public health problem in many parts of the world. It is currently the second leading cause of death in the United States (1,2). Breast cancer, is the most frequently occurring cancer in women and some cases show slow growth with excellent prognosis, while aggressive tumors have poor prognosis (1-3). Breast tumors have also been identified into different subtypes based on the expression of estrogen receptors (ER), progesterone receptors (PR) and Her2 oncogene. The breast tumors that do not express ER, PR or Her2 are called triple-negative breast cancers and ~15% of the breast cancers fall into this category (3,4).Apoptosis is a process of programmed cell death that occurs in response to environmental stimuli and normal gro...

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Doxorubicin Changes Bax /Bcl-xL Ratio, Caspase-8 and 9 in Breast Cancer Cells

Cited by 121 publications

References 55 publications

Effects of Co-Chemotherapy Ethyl Acetate Fraction of Eurycoma Longifolia Jack Roots and Doxorubicin Against Apoptosis Through Expression P53 Mutant and BCL-2

Effects of Co-Chemotherapy Ethyl Acetate Fraction of Eurycoma Longifolia Jack Roots and Doxorubicin Against Apoptosis Through Expression P53 Mutant and BCL-2

Correlation between TRAIL and caspase-8 expression and their relationship with cell proliferation and apoptosis in human osteosarcoma

Apoptotic effect of noscapine in breast cancer cell lines

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