PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation

Appierto, Valentina; Tiberio, Paola; Villani, Maria Grazia; Cavadini, Elena; Formelli, Franca

doi:10.1093/carcin/bgp067

Cited by 61 publications

(55 citation statements)

References 39 publications

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“…This is in agreement with previous reports that in Toxoplasma gondii infection, ROS-triggered trophoblast apoptosis is initiated by ER stress via activation of the JNK pathway along with caspase-12 and CHOP (52). A study demonstrated that fenretinide, a synthetic retinoid with antitumor activity, induced PLAB protein upregulation involving ROS generation, ER stress induction, and JNK activation (53). The role of ROS in TNFinduced apoptosis is also well known (54).…”

Section: Discussionsupporting

confidence: 91%

Liposomal Cholesterol Delivery Activates the Macrophage Innate Immune Arm To Facilitate Intracellular Leishmania donovani Killing

et al. 2014

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Leishmania donovani causes visceral leishmaniasis (VL) by infecting the monocyte/macrophage lineage and residing inside specialized structures known as parasitophorous vacuoles. The protozoan parasite has adopted several means of escaping the host immune response, with one of the major methods being deactivation of host macrophages. Previous reports highlight dampened macrophage signaling, defective antigen presentation due to increased membrane fluidity, and the downregulation of several genes associated with L. donovani infection. We have reported previously that the defective antigen presentation in infected hamsters could be corrected by a single injection of a cholesterol-containing liposome. Here we show that cholesterol in the form of a liposomal formulation can stimulate the innate immune arm and reactivate macrophage function. Augmented levels of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI), along with proinflammatory cytokines such as tumor necrosis factor alpha (TNF-␣) and interleukin 6 (IL-6), corroborate intracellular parasite killing. Cholesterol incorporation kinetics is favored in infected macrophages more than in normal macrophages. Such an enhanced cholesterol uptake is associated with preferential apoptosis of infected macrophages in an endoplasmic reticulum (ER) stress-dependent manner. All these events are coupled with mitogen-activated protein (MAP) kinase activation, while inhibition of such pathways resulted in increased parasite loads. Hence, liposomal cholesterol is a potential facilitator of the macrophage effector function in favor of the host, independently of the T-cell arm.

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Section: Discussionsupporting

confidence: 91%

Liposomal Cholesterol Delivery Activates the Macrophage Innate Immune Arm To Facilitate Intracellular Leishmania donovani Killing

et al. 2014

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“…There is an integrated system to clear ROS in the body to keep balance. Oxidation of cell membrane phospholipids, enzymes and DNA (37,38) by high levels of ROS can alter the function of signal transduction pathways, platelet aggregation, immune control, and the regulation of cell growth, and can also cause necrosis or apoptosis (39,40). Since the generation of ROS is the result of disordered mitochondria function and metabolite augmentation, there may be ways to regulate ROS selectively in cancer cells (41).…”

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis by casticin in cervical cancer cells through reactive oxygen species-mediated mitochondrial signaling pathways

Chen

Cao

Tian³

et al. 2011

Oncol Rep

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Abstract. Casticin, one of the main components from Fructus Viticis, has been reported to inhibit the growth of various cancer cells, including the human cervical cancer cell line HeLa. The purpose of this study was to examine the apoptotic activity and molecular mechanism of casticin action on human cervical cancer cells. The apoptotic activity of casticin on human cervical cancer HeLa, CasKi, SiHa and peripheral blood mononuclear cells (PBMCs) was measured using a histone/DNA ELISA assay, flow cytometry with propidium iodide (PI) staining and DNA agarose gel electrophoresis. The mitochondrial membrane potential and reactive oxygen species (ROS) production were evaluated by flow cytometry analysis. Caspase activities were assayed using a caspase colorimetric activity assay kit. Protein expression levels of cytochrome c, Bax, Bcl-2, Bcl-xL and XIAP were analyzed by Western blotting. Casticin caused accumulation of the Sub-G1 cells and increased reactive oxygen species (ROS) production in HeLa, CasKi, SiHa cell lines, but not in PBMCs. Apoptosis of HeLa cells was induced by casticin via mitochondrial release of cytochrome c due to the reduction of mitochondrial trans membrane potential, activation of caspase-3 and -9, and the production of reactive oxygen species. The pan caspase inhibitor zVAD-FMK, the caspase-9 inhibitor zLEHDfmk and N-acetylcysteine suppressed casticin-induced apoptosis. Bax was upregulated, while expression levels of Bcl-xL and XIAP were downregulated. However, there was no change in the expression of Bcl-2 under the same treatment. Our results indicate that casticin-induced apoptosis of cervical cancer cells is mediated by ROS generation and mitochondrial signaling pathways.

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“…There is an integrated system of clearing ROS in the body to keep balance. Oxidation of cell membrane phospholipids, enzyme, and DNA [24][25][26][27] by high levels of ROS can alter function of signal transduction, platelet aggregation, immune control, and the regulation of cell growth, and they can also cause necrosis or apoptosis [28][29][30][31]. As the generation of ROS is the result of disordered functioning of mitochondria and metabolite augmentation, there may be ways to regulate ROS selectively in cancer cells [12,32].…”

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

Zeng¹,

Tian²,

Liu³

et al. 2012

ABBS

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Casticin, a polymethoxyflavone from Fructus viticis used as an anti-inflammatory agent in Chinese traditional medicine, has been reported to have anti-cancer activity. The purpose of this study was to examine the apoptotic activity of casticin on human cervical cancer cells and its molecular mechanism. We revealed a novel mechanism by which casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by casticin is mediated through generation of reactive oxygen species (ROS) and sustained activation of c-Jun N-terminal kinase (JNK) in HeLa cells. Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and cJun protein. Pre-treatment with N-acetylcysteine and SP600125 effectively attenuated induction of apoptosis by casticin in HeLa cells. Moreover, casticin induced ROS production and apoptotic cell death in other cervical cancer cell lines, such as CasKi and SiHa. Importantly, casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells. These results suggest that ROS generation and sustained JNK activation by casticin play a role in casticin-induced apoptosis and raise the possibility that treatment with casticin might be promising as a new therapy against human cervical cancer.

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PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation

Cited by 61 publications

References 39 publications

Liposomal Cholesterol Delivery Activates the Macrophage Innate Immune Arm To Facilitate Intracellular Leishmania donovani Killing

Liposomal Cholesterol Delivery Activates the Macrophage Innate Immune Arm To Facilitate Intracellular Leishmania donovani Killing

Induction of apoptosis by casticin in cervical cancer cells through reactive oxygen species-mediated mitochondrial signaling pathways

Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

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