Corrigendum to “Oleuropein-Induced Apoptosis Is Mediated by Mitochondrial Glyoxalase 2 in NSCLC A549 Cells: A Mechanistic Inside and a Possible Novel Nonenzymatic Role for an Ancient Enzyme”

Oleuropein (OP) is a bioactive compound derived from plants of the genus Oleaceae exhibiting antitumor properties in several human cancers, including non-small-cell lung cancer (NSCLC). Recent evidence suggests that OP has proapoptotic effects on NSCLC cells via the mitochondrial apoptotic pathway. However, the exact molecular mechanisms behind the apoptogenic action of OP in NSCLC are still largely unknown. Glyoxalase 2 (Glo2) is an ancient enzyme belonging to the glyoxalase system involved in the detoxification of glycolysis-derived methylglyoxal. However, emerging evidence suggests that Glo2 may have also nonenzymatic roles in some malignant cells. In the present study, we evaluated whether and how Glo2 participated in the proapoptotic effects of OP in NSCLC A549 cells. Our results indicate that OP is able to induce apoptosis in A549 cells through the upregulation of mitochondrial Glo2 (mGlo2), mediated by the superoxide anion and Akt signaling pathway. Moreover, our data shows that the proapoptotic role of mGlo2, observed following OP exposure, occurs via the interaction of mGlo2 with the proapoptotic Bax protein. Conversely, OP does not alter the behavior of nonmalignant human BEAS-2B cells or mGlo2 expression, thus suggesting a specific anticancer role for this bioactive compound in NSCLC. Our data identify a novel pathway through which OP exerts a proapoptotic effect in NSCLC and suggest, for the first time, a novel, nonenzymatic antiapoptotic role for this ancient enzyme in NSCLC.

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VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170912115441 ◽

2018 ◽

Vol 18 (2) ◽

pp. 255-262 ◽

Cited By ~ 5

Author(s):

Aikebaier Maimaiti ◽

Amier Aili ◽

Hureshitanmu Kuerban ◽

Xuejun Li

Keyword(s):

Western Blot ◽

Cell Viability ◽

Gallic Acid ◽

Molecular Mechanisms ◽

A549 Cells ◽

Dependent Manner ◽

Lung Carcinoma Cells ◽

Induced Apoptosis ◽

The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

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Rare Chromone Derivatives from the Marine-Derived Penicillium citrinum with Anti-Cancer and Anti-Inflammatory Activities

Marine Drugs ◽

10.3390/md19010025 ◽

2021 ◽

Vol 19 (1) ◽

pp. 25

Author(s):

Yi-Cheng Chu ◽

Chun-Hao Chang ◽

Hsiang-Ruei Liao ◽

Ming-Jen Cheng ◽

Ming-Der Wu ◽

...

Keyword(s):

A549 Cells ◽

Penicillium Citrinum ◽

Signaling Cascades ◽

Human Neutrophils ◽

Cytotoxic Activities ◽

Western Blot Assay ◽

Chromone Derivatives ◽

Anti Cancer ◽

Ic50 Values ◽

Induced Apoptosis

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC50 values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC50 values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.

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P38 MAP kinase is involved in oleuropein-induced apoptosis in A549 cells by a mitochondrial apoptotic cascade

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.09.072 ◽

2017 ◽

Vol 95 ◽

pp. 1425-1435 ◽

Cited By ~ 9

Author(s):

Shasha Cao ◽

Xixi Zhu ◽

Linfang Du

Keyword(s):

Map Kinase ◽

A549 Cells ◽

P38 Map Kinase ◽

Induced Apoptosis ◽

Apoptotic Cascade

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Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression

Biochemical Journal ◽

10.1042/bj20050533 ◽

2005 ◽

Vol 391 (3) ◽

pp. 503-511 ◽

Cited By ~ 27

Author(s):

Natalia V. Oleinik ◽

Natalia I. Krupenko ◽

David G. Priest ◽

Sergey A. Krupenko

Keyword(s):

Cancer Cells ◽

Ectopic Expression ◽

A549 Cells ◽

Dominant Negative ◽

G1 Arrest ◽

Transactivation Domain ◽

Downstream Target ◽

Formyltetrahydrofolate Dehydrogenase ◽

Induced Apoptosis ◽

Hct116 Cells

A folate enzyme, FDH (10-formyltetrahydrofolate dehydrogenase; EC 1.5.1.6), is not a typical tumour suppressor, but it has two basic characteristics of one, i.e. it is down-regulated in tumours and its expression is selectively cytotoxic to cancer cells. We have recently shown that ectopic expression of FDH in A549 lung cancer cells induces G1 arrest and apoptosis that was accompanied by elevation of p53 and its downstream target, p21. It was not known, however, whether FDH-induced apoptosis is p53-dependent or not. In the present study, we report that FDH-induced suppressor effects are strictly p53-dependent in A549 cells. Both knockdown of p53 using an RNAi (RNA interference) approach and disabling of p53 function by dominant-negative inhibition with R175H mutant p53 prevented FDH-induced cytotoxicity in these cells. Ablation of the FDH-suppressor effect is associated with an inability to activate apoptosis in the absence of functional p53. We have also shown that FDH elevation results in p53 phosphorylation at Ser-6 and Ser-20 in the p53 transactivation domain, and Ser-392 in the C-terminal domain, but only Ser-6 is strictly required to mediate FDH effects. Also, translocation of p53 to the nuclei and expression of the pro-apoptotic protein PUMA (Bcl2 binding component 3) was observed after induction of FDH expression. Elevation of FDH in p53 functional HCT116 cells induced strong growth inhibition, while growth of p53-deficient HCT116 cells was unaffected. This implies that activation of p53-dependent pathways is a general downstream mechanism in response to induction of FDH expression in p53 functional cancer cells.

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Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate

Scientific Reports ◽

10.1038/s41598-021-03352-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Urszula K. Komarnicka ◽

Barbara Pucelik ◽

Daria Wojtala ◽

Monika K. Lesiów ◽

Grażyna Stochel ◽

...

Keyword(s):

A549 Cells ◽

Ros Generation ◽

Dependent Manner ◽

Hacat Cells ◽

Icp Ms ◽

Intracellular Ros ◽

M Phase ◽

Lung Adenocarcinoma A549 ◽

Induced Apoptosis

Abstract[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH3-Ph)2CH2SarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex—is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei. A precise cytometric analysis revealed a predominance of apoptosis over the other types of cell death. In the case of HaCaT cells, the overall cytotoxicity was significantly lower, indicating the selective activity of 1-MPSG towards cancer cells. Apoptosis also manifested itself in a decrease in mitochondrial membrane potential along with the activation of caspases-3/9. Moreover, the caspase inhibitor (Z-VAD-FMK) pretreatment led to decreased level of apoptosis (more pronouncedly in A549 cells than in non-cancerous HaCaT cells) and further validated the caspases dependence in 1-MPSG-induced apoptosis. Furthermore, the 1-MPSG complex presumably induces the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. It was also observed that the 1-MPSG mediated intracellular ROS alterations in A549 and HaCaT cells. These results, proved by fluorescence spectroscopy, and flow cytometry, suggest that investigated Cu(I) compound may trigger apoptosis also through ROS generation.

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Abrogation of ER stress-induced apoptosis of alveolar epithelial cells by angiotensin 1–7

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00001.2013 ◽

2013 ◽

Vol 305 (1) ◽

pp. L33-L41 ◽

Cited By ~ 29

Author(s):

Bruce D. Uhal ◽

Hang Nguyen ◽

MyTrang Dang ◽

Indiwari Gopallawa ◽

Jing Jiang ◽

...

Keyword(s):

Epithelial Cells ◽

Er Stress ◽

Cathepsin D ◽

Primary Cultures ◽

A549 Cells ◽

Surfactant Protein ◽

Alveolar Epithelial Cells ◽

Alveolar Epithelial ◽

Induced Apoptosis ◽

Jnk Activation

Earlier work showed that apoptosis of alveolar epithelial cells (AECs) in response to endogenous or xenobiotic factors is regulated by autocrine generation of angiotensin (ANG) II and its counterregulatory peptide ANG1–7. Mutations in surfactant protein C (SP-C) induce endoplasmic reticulum (ER) stress and apoptosis in AECs and cause lung fibrosis. This study tested the hypothesis that ER stress-induced apoptosis of AECs might also be regulated by the autocrine ANGII/ANG1–7 system of AECs. ER stress was induced in A549 cells or primary cultures of human AECs with the proteasome inhibitor MG132 or the SP-C BRICHOS domain mutant G100S. ER stress activated the ANGII-generating enzyme cathepsin D and simultaneously decreased the ANGII-degrading enzyme ACE-2, which normally generates the antiapoptotic peptide ANG1–7. TAPI-2, an inhibitor of ADAM17/TACE, significantly reduced both the activation of cathepsin D and the loss of ACE-2. Apoptosis of AECs induced by ER stress was measured by assays of mitochondrial function, JNK activation, caspase activation, and nuclear fragmentation. Apoptosis induced by either MG132 or the SP-C BRICHOS mutant G100S was significantly inhibited by the ANG receptor blocker saralasin and was completely abrogated by ANG1–7. Inhibition by ANG1–7 was blocked by the specific mas antagonist A779. These data show that ER stress-induced apoptosis is mediated by the autocrine ANGII/ANG1–7 system in human AECs and demonstrate effective blockade of SP-C mutation-induced apoptosis by ANG1–7. They also suggest that therapeutic strategies aimed at administering ANG1–7 or stimulating ACE-2 may hold potential for the management of ER stress-induced fibrotic lung disorders.

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Oridonin Sensitizes Cisplatin-Induced Apoptosis via AMPK/Akt/mTOR-Dependent Autophagosome Accumulation in A549 Cells

Frontiers in Oncology ◽

10.3389/fonc.2019.00769 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Huahong Yang ◽

Yun Gao ◽

Xiaoye Fan ◽

Xingkai Liu ◽

Liping Peng ◽

...

Keyword(s):

A549 Cells ◽

Induced Apoptosis

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Mitochondrial Division Inhibitor 1 Attenuates Mitophagy in a Rat Model of Acute Lung Injury

BioMed Research International ◽

10.1155/2019/2193706 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Xu Luo ◽

Ruimeng Liu ◽

Zhihao Zhang ◽

Zhugui Chen ◽

Jian He ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Mitochondrial Dysfunction ◽

Cell Damage ◽

A549 Cells ◽

Oxygenation Index ◽

Lipid Peroxides ◽

Dry Weight ◽

Induced Apoptosis

The regulation of intracellular mitochondria degradation is mediated by mitophagy. While studies have shown that mitophagy can lead to mitochondrial dysfunction and cell damage, the role of Mdivi-1 and mitophagy remains unclear in acute lung injury (ALI) pathogenesis. In this study, we demonstrated that Mdivi-1, which is widely used as an inhibitor of mitophagy, ameliorated acute lung injury assessed by HE staining, pulmonary microvascular permeability assay, measurement of wet/dry weight (W/D) ratio, and oxygenation index (PaO2/FiO2) analysis. Then, the mitophagy related proteins were evaluated by western blot. The results indicated that LPS-induced activation of mitophagy was inhibited by Mdivi-1 treatment. In addition, we found that Mdivi-1 protected A549 cells against LPS-induced mitochondrial dysfunction. We also found that Mdivi-1 reduced pulmonary cell apoptosis in the LPS-challenged rats and protected pulmonary tissues from oxidative stress (represented by the content of superoxide dismutase, malondialdehyde and lipid peroxides in lung). Moreover, Mdivi-1 treatment ameliorated LPS-induced lung inflammatory response and cells recruitment. These findings indicate that Mdivi-1 mitigates LPS-induced apoptosis, oxidative stress, and inflammation in ALI, which may be associated with mitophagy inhibition. Thus, the inhibition of mitophagy may represent a potential therapy for treating ALI.

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