Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species–Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells

Rithanya, Prabakaran; Ezhilarasan, Devaraj

doi:10.1007/s12029-020-00370-7

Cited by 13 publications

(4 citation statements)

References 41 publications

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“…Some of the results of our molecular analyses also deviate from expectations related to apoptosis. Reactive oxygen species (ROS) accumulation in the cells is one of the mechanisms by which HDACi treatments are known to activate apoptosis [ 61 , 65 ]. We have also observed p53 cytoplasmic expression in differentiated teratoma components, and p53 may induce mitochondrial ROS production in order to activate apoptosis, usually due to genotoxic stress [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

Krasić

Škara

Ulamec

et al. 2020

Cancers

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Among testicular germ cell tumors, teratomas may often be very aggressive and therapy-resistant. Our aim was to investigate the impact of histone deacetylase inhibitors (HDACi) on the in vitro growth of experimental mouse teratoma by treating their embryonic source, the embryo-proper, composed only of the three germ layers. The growth of teratomas was measured for seven days, and histopathological analysis, IHC/morphometry quantification, gene enrichment analysis, and qPCR analysis on a selected panel of pluripotency and early differentiation genes followed. For the first time, within teratomas, we histopathologically assessed the undifferentiated component containing cancer stem cell-like cells (CSCLCs) and differentiated components containing numerous lymphocytes. Mitotic indices were higher than apoptotic indices in both components. Both HDACi treatments of the embryos-proper significantly reduced teratoma growth, although this could be related neither to apoptosis nor proliferation. Trichostatin A increased the amount of CSCLCs, and upregulated the mRNA expression of pluripotency/stemness genes as well as differentiation genes, e.g., T and Eomes. Valproate decreased the amount of CSCLCs, and downregulated the expressions of pluripotency/stemness and differentiation genes. In conclusion, both HDACi treatments diminished the inherent tumorigenic growth potential of the tumor embryonal source, although Trichostatin A did not diminish the potentially dangerous expression of cancer-related genes and the amount of CSCLC.

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Section: Discussionmentioning

confidence: 99%

Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

Krasić

Škara

Ulamec

et al. 2020

Cancers

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“…The antiepileptic properties of VPA have been associated with its ability to inhibit the degradation of gamma-aminobutyric acid (GABA). Also, it is used as an antineoplastic agent via its histone deacetylase inhibition [2]. Long-term use of VPA has been reported to have some toxic and/or side effects on several organs such as the liver [3], kidney [4], and testis [5].…”

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confidence: 99%

Protective effect of edaravone on rat testis after valproic acid treatment

CELIK¹,

Bayrak²,

Cakmak³

et al. 2022

jrp

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Valproic acid (n-dipropyl-acetic acid, VPA) is a medication used as anticonvulsant in the treatment of bipolar disorder, and for migraine prophylaxis. Long-term use of VPA is known to trigger reproductive impairment, which is mediated by elevation of testicular oxidative stress. Edaravone is used in the treatment of cerebrovascular diseases. It can diffuse into many disease-affected organs, thus shows protective effects in numerous tissues including the heart, lung, and testis. The main goal of the present study was to determine the possible protective role of edaravone against VPA-induced oxidative testicular injury. Male Sprague Dawley rats were assigned into four groups. Control rats; rats given only edaravone (30 mg/kg/day); rats given only VPA (500 mg/kg/day); rats given VPA+edaravone for seven days. Edaravone and VPA were applied intraperitoneally. After eight days, testicular tissues were taken from rats. There was a statistically significant increase in the levels of reduced glutathione, lipid peroxidation, reactive oxygen species, total oxidant status, oxidative stress index, and DNA contents as well as catalase, superoxide dismutase, glutathione-related enzymes, gamma-glutamyl transferase, acid and alkaline phosphatases, lactate dehydrogenase, myeloperoxidase and sorbitol dehydrogenase activities in VPA group. More so, advanced oxidized protein products, protein carbonyl, and nitric oxide levels were also significantly increased in VPA group. Activities of glucose-6phosphate dehydrogenase and sodium/potassium ATPase and total antioxidant status levels remarkably decreased in VPA given group. Treatment with edaravone to VPA group significantly reverted these alterations. These findings demonstrate that administration of edaravone has a beneficial effect against testicular injury in VPA-induced oxidative stress.

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“…Conventional anti-cancer therapies with standard chemotherapeutic agents have various adverse effects [5]. It includes nausea, vomiting, metallic taste, hair loss, etc [6]. Nanotechnology has played an important role in cancer treatment [7,8].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effect of Lippia nodiflora Leaf Extract against the Prostate Cancer Cell Line

Sharmila

Elumalai

Subramanian

et al. 2021

JPRI

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Prostate cancer is the second most common cause of cancer deaths for men. Lippia. Nodiflora (L. nodiflora) has been used as a natural remedy for various diseases, because of its antioxidant, anti-inflammatory, anti-bacterial, and anti-tumor effect. This study was to investigate the cytotoxic effect of L. nodiflora ethanolic leaf extract in prostate cancer cell lines (PC-3). The growth inhibitory effect of L. nodiflora ethanolic leaf extract was assessed by MTT assay. The cell morphological changes in L. nodiflora leaf extract-treated cells were observed using an inverted phase-contrast microscope. Apoptosis induction by L. nodiflora was determined by AO/EtBr (acridine orange and ethidium bromide) dual staining. MTT test results showed dose-dependent cell growth inhibition in PC-3 cells treated with L. nodiflora leaf extract (10-120 µg/mL). The IC-50 dose was observed at 40µg/ml. Morphological changes such as reduction in the number of cells, cell shrinkage, and cytoplasmic membrane blebbing were observed in the treated cells. Induction of apoptosis by L. nodiflora (40µg/ml) treated cells showed an increased number of early apoptotic and late apoptotic cells. The above data indicate that L. nodiflora inhibits cell proliferation and induces apoptosis in prostate cancer cells. Therefore, it can be concluded that L. nodiflora exhibits anti-cancer activity, and thus it raises new hope for its use in anti-cancer therapy.

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Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species–Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells

Cited by 13 publications

References 41 publications

Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

Protective effect of edaravone on rat testis after valproic acid treatment

Cytotoxic Effect of Lippia nodiflora Leaf Extract against the Prostate Cancer Cell Line

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