Verrucarin A induces apoptosis through ROS-mediated EGFR/MAPK/Akt signaling pathways in MDA-MB-231 breast cancer cells

Palanivel, K.; Kanimozhi, Veerasamy; Kadalmani, Balamuthu; Akbarsha, Mohammad Abdulkader

doi:10.1002/jcb.24874

Cited by 26 publications

(26 citation statements)

References 21 publications

(25 reference statements)

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“…Moreover, evidence from earlier studies show that there seems to be a hierarchy in the relationship between ROS and Akt, in which ROS tends to function as an upstream signal for Akt [24,45,46]. In the current study, we demonstrated for the first time that both the activity of PI3k/Akt pathway and the cellular redox state are closely related to the pharmacological effect of Deguelin.…”

Section: Discussionsupporting

confidence: 62%

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Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway

Ding

et al. 2015

Cancer Cell Int

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BackgroundDuguelin is a rotenoid extracted from plants and has potent antitumor effects in vitro and in vivo. However, the mechanism underlying the antitumor effect remains unclear. Our preliminary study showed that Deguelin is effective to stimulate the generation of Reactive Oxygen Species (ROS). In the current study, we evaluated the in vitro cytotoxicity of Deguelin against lung cancer cells and studied whether a ROS scavenger, N-acetyl-cysteine (NAC), can reverse the inhibitory effect of Deguelin.ResultsWe showed that the dose-dependent apoptotic inducing effect of Deguelin could be partially reversed by the co-administration of NAC. Moreover, Deguelin reduced the phosphorylation of Akt protein and induced the apoptotic protein Caspase-3 in a dose-dependent manner. Co-treatment with NAC partially attenuated this effect and rescued some cells from apoptosis.ConclusionDeguelin induces the apoptosis of cancer cells through a ROS driven Akt pathway, which could translate into a promising therapeutic for lung cancer.

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Section: Discussionsupporting

confidence: 62%

“…As previously reported, tumor cells are vulnerable to the induced ROS generation due to the insufficiency of antioxidant mechanisms [24,27]. Intracellular ROS accumulation by some chemotherapeutics is one of the most important strategies of inducing the apoptosis of cancer cells [28,29].…”

Section: Discussionmentioning

confidence: 99%

Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway

Ding

et al. 2015

Cancer Cell Int

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“…p38MAPK and ERK are two important proteins in the MAPK pathway, and MAPK/AKT has been associated with multiple kind of cancers by modulating tumor cells proliferation, apoptosis, and metastasis [30-32]. Similar, Wnt/β-Catenin has also been reported as a pivotal regulator of tumor cells metastasis [33-35].…”

Section: Discussionmentioning

confidence: 99%

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

Zhang

Feng

2017

Cell Physiol Biochem

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Background/Aims: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously. Methods: The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay. Results: MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells. Conclusion: This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.

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“…70,71 However, fewer reports describe p38- or JNK-mediated signaling as part of the molecular mechanism of drug-induced DNA damage. 1,21 We and others have previously demonstrated a link between AhR signaling and the ability of 5F 203 to mediate DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Ligand 5F 203 Induces Oxidative Stress That Triggers DNA Damage in Human Breast Cancer Cells

McLean¹,

Watkins²,

Campbell³

et al. 2015

Chem. Res. Toxicol.

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Breast tumors often show profound sensitivity to exogenous oxidative stress. Investigational agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) induces aryl hydrocarbon receptor (AhR)-mediated DNA damage in certain breast cancer cells. Since AhR agonists often elevate intracellular oxidative stress, we hypothesize that 5F 203 increases reactive oxygen species (ROS) to induce DNA damage, which thwarts breast cancer cell growth. We found that 5F 203 induced single-strand break formation. 5F 203 enhanced oxidative DNA damage that was specific to breast cancer cells sensitive to its cytotoxic actions, as it did not increase oxidative DNA damage or ROS formation in nontumorigenic MCF-10A breast epithelial cells. In contrast, AhR agonist and procarcinogen benzo[a]pyrene and its metabolite, 1,6-benzo[a]pyrene quinone, induced oxidative DNA damage and ROS formation, respectively, in MCF-10A cells. In sensitive breast cancer cells, 5F 203 activated ROS-responsive kinases: c-Jun-N-terminal kinase (JNK) and p38 mitogen activated protein kinase (p38). AhR antagonists (alpha-naphthoflavone, CH223191) or antioxidants (N-acetyl-l-cysteine, EUK-134) attenuated 5F 203-mediated JNK and p38 activation, depending on the cell type. Pharmacological inhibition of AhR, JNK, or p38 attenuated 5F 203-mediated increases in intracellular ROS, apoptosis, and single-strand break formation. 5F 203 induced the expression of cytoglobin, an oxidative stress-responsive gene and a putative tumor suppressor, which was diminished with AhR, JNK, or p38 inhibition. Additionally, 5F 203-mediated increases in ROS production and cytoglobin were suppressed in AHR100 cells (AhR ligand-unresponsive MCF-7 breast cancer cells). Our data demonstrate 5F 203 induces ROS-mediated DNA damage at least in part via AhR, JNK, or p38 activation and modulates the expression of oxidative stress-responsive genes such as cytoglobin to confer its anticancer action.

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Verrucarin A induces apoptosis through ROS-mediated EGFR/MAPK/Akt signaling pathways in MDA-MB-231 breast cancer cells

Cited by 26 publications

References 21 publications

Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway

Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

Aryl Hydrocarbon Receptor Ligand 5F 203 Induces Oxidative Stress That Triggers DNA Damage in Human Breast Cancer Cells

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