Natural daucane esters induces apoptosis in leukaemic cells through ROS production

Dall’Acqua, Stefano; Linardi, Maria Antonella; Bortolozzi, Roberta; Clauser, Maria; Marzocchini, Sara; Maggi, Filippo; Nicoletti, Marcello; Innocenti, Gabbriella; Basso, Giuseppe; Viola, Giampietro

doi:10.1016/j.phytochem.2014.09.001

Cited by 22 publications

(11 citation statements)

References 38 publications

(43 reference statements)

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“…In addition, mitochondrial fragmentation can activate cell death via two mechanisms [ 15 ]; one mechanism is driven via HK2/VDAC1 disassociation-mediated mPTP opening, and the other involves mROS-induced cardiolipin oxidation. Notably, mitochondrial ROS (mROS) overloading, as a primary result of mitochondrial fragmentation [ 16 ], has been noted in different disease models such as those of gastric cancer [ 17 ], breast cancer [ 18 ], and leukemia [ 19 ]. Subsequently, excessive mitochondrial oxidative injury can activate the HtrA2/Omi-related apoptotic pathway in a manner that is dependent on caspase-9 activity [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

et al. 2018

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BackgroundMitochondrial fragmentation drastically regulates the viability of pancreatic cancer through a poorly understood mechanism. The present study used erlotinib to activate mitochondrial fragmentation and then investigated the downstream events that occurred in response to mitochondrial fragmentation.MethodsCell viability and apoptosis were determined via MTT assay, TUNEL staining and ELISA. Mitochondrial fragmentation was measured via an immunofluorescence assay and qPCR. siRNA transfection and pathway blockers were used to perform the loss-of-function assays.ResultsThe results of our study demonstrated that erlotinib treatment mediated cell apoptosis in the PANC-1 pancreatic cancer cell line via evoking mitochondrial fragmentation. Mechanistically, erlotinib application increased mitochondrial fission and reduced mitochondrial fusion, triggering mitochondrial fragmentation. Subsequently, mitochondrial fragmentation caused the overproduction of mitochondrial ROS (mROS). Interestingly, excessive mROS induced cardiolipin oxidation and mPTP opening, finally facilitating HtrA2/Omi liberation from the mitochondria into the cytoplasm, where HtrA2/Omi activated caspase-9-dependent cell apoptosis. Notably, neutralization of mROS or knockdown of HtrA2/Omi attenuated erlotinib-mediated mitochondrial fragmentation and favored cancer cell survival.ConclusionsTogether, our results identified the mROS-HtrA2/Omi axis as a novel signaling pathway that is activated by mitochondrial fragmentation and that promotes PANC-1 pancreatic cancer cell mitochondrial apoptosis in the presence of erlotinib.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0665-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

et al. 2018

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“…For this reason a commonly used strategy for killing cancer cells consists of using ionizing radiation and/or chemotherapeutic drugs that induce the generation of these oxidants to levels that are capable of triggering apoptosis once ROS levels reach or exceed a certain threshold within the cell. The rationale for this approach relies on the fact that since cancer cells already have high levels of endogenous ROS prior to treatment they should reach this apoptotic threshold faster/easier compared to normal cells [ 166 , 167 ].…”

Section: Ros Inducing Chemotherapymentioning

confidence: 99%

“…GSH is an abundant cellular antioxidant that plays a key role in cellular REDOX homeostasis as already described in this review. Inhibition of glutathione reductase leads to the build-up of oxidized glutathione (GSSG) that can no longer exert its antioxidant function; as a consequence a significant accumulation of ROS within the cell is observed, driving caspase-3 activation and apoptosis [ 166 , 169 , 170 ].…”

Section: Ros Inducing Chemotherapymentioning

confidence: 99%

The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

Castaldo

Freitas

Conchinha

et al. 2015

Oxidative Medicine and Cellular Longevity

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The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

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“…Intracellular ROS accumulation by some chemotherapeutics is one of the most important strategies of inducing the apoptosis of cancer cells [44]. High levels of ROS triggered mitochondrial permeability transition pore opening, which has been described as an important downstream signal of ROS, and the release of pro-apoptotic factors and the activation of caspase-3 [45]. In the current study, DDSD exerted an oxidative stress on B16F10 cells by elevating the intracellular level of ROS, which was partially reversed by co-treatment with the antioxidant NAC (Figure 3c).…”

Section: Discussionmentioning

confidence: 99%

Spatane diterpinoid from the brown algae, Stoechospermum marginatum induces apoptosis via ROS induced mitochondrial mediated caspase dependent pathway in murine B16F10 melanoma cells

Velatooru

Baggu

Janapala

2016

Molecular Carcinogenesis

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Spatane diterpinoids isolated from the brown marine algae Stoechospermum marginatum were known to have cytotoxic effects in human cancerous cell lines and murine melanoma cells; the underling apoptotic mechanism of diterpinoids still remains unclear so far. Thus, in the present study, the apoptotic mechanism of a spatane diterpinoid, 5(R), 19-diacetoxy-15,18(R and S), dihydro spata-13, 16(E)-diene (DDSD) was investigated mainly in B16F10 melanoma cells because they were most susceptible to DDSD than THP1, U937, COLO205, and HL60 cells. The treatment of B6F10 cells with DDSD resulted in morphological alterations, nuclear condensation, and DNA fragmentation, which leads to cell growth inhibition in a concentration-dependent manner. Data indicate that DDSD induced the generation of ROS, consequentially caused alteration in Bax/Bcl-2 ratio that disrupted the inner mitochondrial transmembrane potential (ΔΨm) resulting in cytochrome c redistribution to the cytoplasm and activation of caspase-mediated apoptotic pathway. Flow cytometric analysis clearly indicated that the DDSD inducing phosphatidylserine externalization and mediated "S-phase" arrest in cell cycle. In addition, results also found that DDSD induced apoptosis through deregulating PI3K/AKT signaling pathway. The anti-tumor activity of DDSD was evaluated in C57BL/6 mice bearing B16F10 melanoma. It effectively inhibited tumor growth (volume and weight) in a dose dependent manner, yet without apparent toxic effects. Morphology and apoptotic status of tumor tissues in the treated mice were assessed by microscopy and TUNEL assay, respectively. Our study shows a therapeutic potential of DDSD for the treatment of malignant melanoma and a new source of anticancer drugs. © 2016 Wiley Periodicals, Inc.

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Natural daucane esters induces apoptosis in leukaemic cells through ROS production

Cited by 22 publications

References 38 publications

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

RETRACTED ARTICLE: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways

The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

Spatane diterpinoid from the brown algae, Stoechospermum marginatum induces apoptosis via ROS induced mitochondrial mediated caspase dependent pathway in murine B16F10 melanoma cells

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