Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A.
TL;DR: The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 μg/ml.
About: This article is published in Phytomedicine.The article was published on 2012-08-15. It has received 106 citations till now. The article focuses on the topics: Cytochrome c & Apoptosis.
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TL;DR: A significant correlation between age and tumor location with Bax/Bcl-2 expression ratio is indicated, suggesting predictive value as a potential molecular marker of colorectal cancer.
Abstract: Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. Iran. Biomed. J. 19 (2): 69-75, 2015
131 citations
TL;DR: It is demonstrated that puerarin attenuated the neurological deficits, effectively relieves cerebral edema, and reduce BBB disruption in SAH mice, and can be act as a novel therapy for SAH.
125 citations
TL;DR: The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways, and the pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-ap optotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner.
Abstract: Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC50) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G1 phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC25, 98.91% at IC50, and 99.44% at IC75. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways.
91 citations
TL;DR: Accumulated reactive oxygen species and dysregulation of some apoptosis-related genes might ultimately lead to apoptosis in Cisp-resistant SW620 cells, providing new clues for novel and selective chemotherapy on cisplatin-resistant colorectal cancer cells.
86 citations
TL;DR: FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus, concluding that FRT acts as a radioprotector.
Abstract: The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl-2(Ca2+)/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to 60Co γ-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca2+, ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus. FRT significantly reduced cell apoptosis compared with the irradiation group. The expression of Ca2+ and C-Caspase-3 was decreased after FRT treatment compared with the radiation-treated group. At the same time, expression of prototype PARP-1 and Bcl-2 increased, leading to a decrease in the percentage of apoptosis cells in FRT treatment groups. We conclude that FRT acts as a radioprotector. Apoptosis signals were activated via the Bcl-2(Ca2+)/Caspase-3/PARP-1 pathway in irradiated cells and FRT inhibited this pathway of apoptosis by down-regulation of C-Caspase-3 and Ca2+ and up-regulation of prototype PARP-1 and Bcl-2.
83 citations
Cites background from "Involvement of NF-κB and Bcl2/Bax s..."
...For the intrinsic mitochondria-dependent pathway, the release of cytochrome C from mitochondria into the cytosol is fundamental to apoptosome formation and Caspase-3 activation [27]....
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References
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TL;DR: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation and is used to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
50,114 citations
"Involvement of NF-κB and Bcl2/Bax s..." refers methods in this paper
...Viability assay was e 19 (2012) 1007– 1015 done using MTT assay as previously described by Mosmann (1983)....
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TL;DR: In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process.
Abstract: In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.
4,754 citations
TL;DR: This work dedicates this work to Guenter Brueckner, always an inspiration, and to Wayne Fenton for critical reading and Zhaohui Xu for figure preparation.
2,798 citations
"Involvement of NF-κB and Bcl2/Bax s..." refers background in this paper
...HSPs re also known to protect cells from stress by preventing the proein aggregation and promote the refolding of denatured proteins Bukau and Horwich 1998)....
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TL;DR: The generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize are discussed, but also an outlook on their modulation in therapeutics is provided.
Abstract: Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.
2,625 citations
TL;DR: The role of ROS in the regulation of apoptosis, especially in inflammatory cells, is focused on, with particular attention to mitochondria.
Abstract: Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
2,529 citations
"Involvement of NF-κB and Bcl2/Bax s..." refers background in this paper
...c into the cytosol, to triggers caspase-9 activation and initiates the executioner caspases which leads cell to apoptosis (Simon et al. 2000)....
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...…to oxidative DNA damage (Evans et al. 2004; Schumacker 2006) followed by disruption of the mitochondrial membrane potential (MMP) and release of cytochrome c into the cytosol, to triggers caspase-9 activation and initiates the executioner caspases which leads cell to apoptosis (Simon et al. 2000)....
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...There is growing evidence that ROS and mitochondria play an mportant role in apoptosis induction (Simon et al. 2000)....
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