Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

Lee, Hae-Miru; Kim, Soo-Min; Choi, Kyung‐Chul

doi:10.3390/ijerph14080854

Cited by 8 publications

(6 citation statements)

References 55 publications

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“…Since FA is a reactive chemical capable of forming many adverse side reactions in the cell, it is logical that the FA level must be strictly regulated. Interestingly, an increase of FA in certain types of cancer cells appears to be well tolerated 26,30,33,53,54 . To understand features of FA metabolism in normal cells, we probed the effect of increased levels of FA in primary human fibroblasts (FSK).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts

Nadalutti

Stefanick

Zhao

et al. 2020

Sci Rep

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Formaldehyde (FA) is a simple biological aldehyde that is produced inside cells by several processes such as demethylation of DNA and proteins, amino acid metabolism, lipid peroxidation and one carbon metabolism (1-C). Although accumulation of excess FA in cells is known to be cytotoxic, it is unknown if an increase in FA level might be associated with mitochondrial dysfunction. We choose to use primary human fibroblasts cells in culture (foreskin, FSK) as a physiological model to gain insight into whether an increase in the level of FA might affect cellular physiology, especially with regard to the mitochondrial compartment. FSK cells were exposed to increasing concentrations of FA, and different cellular parameters were studied. Elevation in intracellular FA level was achieved and was found to be cytotoxic by virtue of both apoptosis and necrosis and was accompanied by both G2/M arrest and reduction in the time spent in S phase. A gene expression assessment by microarray analysis revealed FA affected FSK cells by altering expression of many genes including genes involved in mitochondrial function and electron transport. We were surprised to observe increased DNA double-strand breaks (DSBs) in mitochondria after exposure to FA, as revealed by accumulation of γH2A.X and 53BP1 at mitochondrial DNA foci. This was associated with mitochondrial structural rearrangements, loss of mitochondrial membrane potential and activation of mitophagy. Collectively, these results indicate that an increase in the cellular level of FA can trigger mitochondrial DNA double-strand breaks and dysfunction. Genome stability is important for maintenance of normal cellular metabolism and is essential for cell survival. During evolution, cells have developed highly conserved mechanisms of DNA repair to prevent genetic alterations due to DNA damage caused by endogenous as well as exogenous sources 1,2. Eukaryotic cells contain two genomes, nuclear and mitochondrial (mtDNA), and it is suggested that oxidative stress in mitochondria will also impose oxidative stress on the nucleus 3-5. Therefore, oxidative stress may impact both genomes in a highly interconnected fashion. Mitochondria are double membrane organelles and generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy for cellular functions by establishing intricate genetic interactions with the nuclear compartment. However, among the approximately 1,200 proteins needed for mitochondrial metabolism, only a few are encoded by the mitochondrial genome 6. The mammalian mitochondrial DNA is a double-stranded, closed-circular molecule assembled into compact structures called nucleoids. The mitochondrial genome encodes 13 proteins that are key components of the oxidative phosphorylation system (OXPHOS), in addition to 2 rRNAs and 22 tRNAs, necessary for the mitochondrial translational machinery 7. OXPHOS is characterized by multimeric complexes, that are responsible for the transfer of electrons to molecular oxygen, leading to protons being pumpe...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts

Nadalutti

Stefanick

Zhao

et al. 2020

Sci Rep

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“…In recent years, a series of studies have begun to explore the mechanism of FA-induced AD pathogenesis. As one of the markers of oxidative stress, the appearance of FA is often accompanied by an increase in ROS and lipid peroxides [ 5 , 9 , 10 , 11 ]. Strong oxidative stress and cytotoxicity can further lead to DNA lesions [ 12 ], endoplasmic reticulum stress (ERS) [ 11 ], and the impairment of mitochondrial function [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment

et al. 2023

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Formaldehyde (FA) has been found to induce major Alzheimer’s disease (AD)-like features including cognitive impairment, Aβ deposition, and Tau hyperphosphorylation, suggesting that it may play a significant role in the initiation and progression of AD. Therefore, elucidating the mechanism underlying FA-induced neurotoxicity is crucial for exploring more comprehensive approaches to delay or prevent the development of AD. Mangiferin (MGF) is a natural C-glucosyl-xanthone with promising neuroprotective effects, and is considered to have potential in the treatment of AD. The present study was designed to characterize the effects and mechanisms by which MGF protects against FA-induced neurotoxicity. The results in murine hippocampal cells (HT22) revealed that co-treatment with MGF significantly decreased FA-induced cytotoxicity and inhibited Tau hyperphosphorylation in a dose-dependent manner. It was further found that these protective effects were achieved by attenuating FA-induced endoplasmic reticulum stress (ERS), as indicated by the inhibition of the ERS markers, GRP78 and CHOP, and downstream Tau-associated kinases (GSK-3β and CaMKII) expression. In addition, MGF markedly inhibited FA-induced oxidative damage, including Ca2+ overload, ROS generation, and mitochondrial dysfunction, all of which are associated with ERS. Further studies showed that the intragastric administration of 40 mg/kg/day MGF for 6 weeks significantly improved spatial learning ability and long-term memory in C57/BL6 mice with FA-induced cognitive impairment by reducing Tau hyperphosphorylation and the expression of GRP78, GSK-3β, and CaMKII in the brains. Taken together, these findings provide the first evidence that MGF exerts a significant neuroprotective effect against FA-induced damage and ameliorates mice cognitive impairment, the possible underlying mechanisms of which are expected to provide a novel basis for the treatment of AD and diseases caused by FA pollution.

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“…As PPC is a rare disease, diagnosis before surgery is di cult [5]. The diagnostic criteria for PPC include a lack of a previous urological malignancy, solitary or predominant lung lesion without a primary gonadal site, elevated serum β-HCG levels that normalize following surgery or chemotherapy, and pathological con rmation of the disease [6].…”

Section: Discussionmentioning

confidence: 99%

“…The patient had a smoking history, which might be a risk factor for choriocarcinoma. It has been reported that formaldehyde and benzene, the main components of cigarette smoke, induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and activation of oxidative stress [5]. However, research also showed that acrylonitrile, one of main components of cigarette smoke, has the potential to induce apoptosis of human choriocarcinoma cancer cells by activating ROS[6].…”

Section: Discussionmentioning

confidence: 99%

Choriocarcinoma syndrome of primary pulmonary choriocarcinoma after lung lobe resection: A case report and review of the literature

Chen

Liu

et al. 2022

Preprint

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Introduction: Primary pulmonary choriocarcinoma (PPC) is extremely rare, especially in males. It is characterized by a poor response to therapy and shortened survival times. Here, we report a PPC case that was complicated by choriocarcinoma syndrome (CS) and present a review of the literature. Case presentation: A 59-year-old man with a 30-pack-year smoking history was referred to our hospital because of haemoptysis and chest pain. Positron emission tomography-computed tomography (PET-CT) showed multiple bilateral pulmonary nodules and multiple metastases throughout the body. The patient underwent single-port thoracoscopic wedge resection of the right lung upper lobe. Histological examinations verified the diagnosis of choriocarcinoma. Three days after the operation, the patient developed massive haemoptysis. A bronchoscopic examination showed bleeding from the bilateral main bronchus. Despite management in the intensive care unit (ICU), the patient died two weeks after surgery. Conclusions For advanced choriocarcinoma cases, minimally invasive or even non-invasive procedures are more suitable to avoid inducing CS. When patients with a high tumour mass and elevated tumour markers, we need to be alert to the occurrence of CS. Surgery and modified chemotherapy, based on the physical condition of the patient, may currently be the best therapy for PPC.

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Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

Cited by 8 publications

References 55 publications

Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts

Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts

The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment

Choriocarcinoma syndrome of primary pulmonary choriocarcinoma after lung lobe resection: A case report and review of the literature

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