The suppression of manganese superoxide dismutase decreased the survival of human glioblastoma multiforme T98G cells

Hardiany, Novi Silvia; Sadikin, Mohamad; Siregar, Nuryati Chairani; Wanandi, Septelia Inawati

doi:10.13181/mji.v26i1.1511

Cited by 11 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike the previous report on ovarian cancer [12], our concomitant study has obtained that the suppression of MnSOD mRNA expression in T98G cells through siRNA transfection could reduce the protein level and enzyme activity and enhance superoxide radicals production, leading to cell death [45]. Hence, we evidently suggest that the impact of oxidative stress induced by high-dose rotenone is most likely associated with low MnSOD expression at the level of protein and enzyme activity.…”

Section: Discussioncontrasting

confidence: 74%

Suppression of Manganese Superoxide Dismutase Activity in Rotenone-Treated Human Glioblastoma T98g Cells Reduces Cell Viability

Wanandi

Hardiany

Siregar

et al. 2018

Asian J Pharm Clin Res

Self Cite

View full text Add to dashboard Cite

Objective: Glioma is the most common human primary brain tumor which is highly resistant to oxidative stress-based anticancer. The aim of this study was to analyze the effect of rotenone-induced reactive oxygen species (ROS) on the modulation of manganese superoxide dismutase (MnSOD) expression and cell viability in human glioblastoma (GBM) T98G cells. Methods:In this in vitro experimental study, T98G cells were treated with high-dose rotenone (0.5, 5, and 50 μM, respectively). Following rotenone treatment and intracellular ROS, both peroxide and superoxide radicals were determined. Moreover, we analyzed MnSOD mRNA expression, protein, and specific activity, as well as cell survival including viability, proliferation, apoptosis, and mitochondrial structure.Results: High-dose rotenone treatment of T98G cells significantly increased intracellular ROS and MnSOD mRNA, but its protein and specific activity definitely decreased. The treatment also led to a reduction of cell viability, enhancement of apoptosis, and disruption of mitochondrial integrity. Conclusion:Overproduction of ROS in rotenone-treated human GBM T98G cells could suppress the MnSOD protein level and activity even though mRNA synthesis has been increased. This modulation led to reduced survival of T98G cells through induction of cell death rather than inhibition of cell proliferation.Keywords: Cell viability, Glioblastoma multiforme, Manganese superoxide dismutase, Rotenone. INTRODUCTIONGlioma is the most common human primary brain tumor which arises from glial cells [1]. Nowadays, the use of conventional treatments such as chemotherapy and radiation does not significantly enhance the life expectancy of glioma patients, particularly those with high-grade malignant (the WHO Grade IV) multiforme glioblastoma (GBM) patients, which is highly resistant to therapy [2]. Combinatorial treatment strategy has been reported to have improved the chemotherapeutic delivery to tumor cells in the brain [3,4]. Nevertheless, accumulating evidence suggests that dysregulation of cell cycle and apoptosis could lead to radiotherapy resistance [5]. A plausible mechanism for this resistance might involve high antioxidant status in tumor cells which could affect cell survival in response to radiation-induced oxidative stress [6].Manganese superoxide dismutase (MnSOD) is a major cellular antioxidant located in the mitochondrial matrix. This enzyme catalyzes the reactive superoxide anion into hydrogen peroxide which will be later eliminated by catalase or peroxidase. The previous studies have reported that the upregulation of MnSOD expression could inhibit the phenotype of various cancer cells, suggesting that MnSOD is a tumor suppressor [7][8][9][10]. However, this assumption is still controversial, since it has been demonstrated that MnSOD was overexpressed in several human cancers including GBM [11]. Furthermore, MnSOD has been reported to have an important role on tumor cell growth and proliferation in ovarian cancer through regulation of superoxide level [12]. Our recent s...

show abstract

Section: Discussioncontrasting

confidence: 74%

Suppression of Manganese Superoxide Dismutase Activity in Rotenone-Treated Human Glioblastoma T98g Cells Reduces Cell Viability

Wanandi

Hardiany

Siregar

et al. 2018

Asian J Pharm Clin Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mRNA expressions of Ki-67, TGF- β 1, and TGF- β 1 receptor were analyzed using qRT-PCR, with β -actin as housekeeping gene. The primer sequences used for Ki-67, Col1A1, and β -actin in this study were as stated in Rahmaniah et al [ 18 ]; primers for TIMP1, TIMP2, MMP2, and MMP9 were from Dai et al [ 19 ]; primers for MnSOD were from Hardiany et al [ 20 ]; primers for GPX were from Dietrich et al [ 21 ]; and the primer sequences for TGF- β 1 and TGF- β 1 receptor are as follows: TGF- β 1 Fwd: 5′-TGAACCGGCCTTTCCTGCTTCTACATG-3′; TGF- β 1 Rev: 5′-GCGGAAGTCAATGTACAGCTGCCGC-3′; TGF- β 1-R Fwd: 5′-TTGCTGGACCAGTGTGCTTCG-3′; TGF- β 1-R Rev: 5′-CCATCTGTTTGGGATATTTGGCC-3′.…”

Section: Methodsmentioning

confidence: 99%

Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways

Lestari

Louisa

Soetikno

et al. 2018

Journal of Toxicology

View full text Add to dashboard Cite

Liver fibrosis is characterized by excessive accumulation of extracellular matrix in chronic liver injury. Alcohol-induced fibrosis may develop into cirrhosis, one of the major causes of liver disease mortality. Previous studies have shown that alpha mangostin can decrease ratio of pSmad/Smad and pAkt/Akt in TGF-β-induced liver fibrosis model in vitro. Further investigation of the mechanism of action of alpha mangostin in liver fibrosis model still needs to be done. The present study aimed to analyze the mechanism of action of alpha mangostin on acetaldehyde induced liver fibrosis model on TGF-β and ERK 1/2 pathways. Immortalized HSCs, LX-2 cells, were incubated with acetaldehyde, acetaldehyde with alpha mangostin (10 and 20 μM), or alpha mangostin only (10 μM). Sorafenib 10 μM was used as positive control. LX-2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on hepatic stellate cells proliferation and activation markers and its possible mechanism of action via TGF-β and ERK1/2 were studied. Acetaldehyde was shown to increase proliferation and expression of profibrogenic and migration markers on HSC, while alpha mangostin treatment resulted in a reduced proliferation and migration of HSC and decreased Ki-67 and pERK 1/2 expressions. These findings were followed with decreased expressions and concentrations of TGF-β; decreased expression of Col1A1, TIMP1, and TIMP3; increased expression of MnSOD and GPx; and reduction in intracellular reactive oxygen species. These effects were shown to be dose dependent. Therefore, we conclude that alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-β and ERK 1/2 pathways.

show abstract

“…Intracellular ROS production was carried out using a superoxide sensitive probe dihydroethidium (DHE) assay (Invitrogen™ Molecular Probes™, Thermo Fisher Scientific Inc., Waltham, MA, USA), as described previously (Hardiany et al, 2017). Briefly, 2 × 10 4 cells were collected and twice washed with sterile phosphate buffer saline (PBS) (Gibco ® , Thermo Fisher Scientific Inc., Waltham, MA, USA).…”

Section: In Vitro Assay For Ros Detectionmentioning

confidence: 99%

“…Annealing temperature for both 18S rRNA and MnSOD primers were 60ºC, meanwhile for survivin primers was 61ºC. The qRT-PCR was performed as previously described Hardiany et al, 2017). All reactions were performed in triplicate and relative mRNA expression levels were calculated using Livak formula.…”

Section: Total Rna Preparation and Real-time Rt-pcrmentioning

confidence: 99%

See 1 more Smart Citation

Suppression of Rotenone-Treated Human Breast Cancer Stem Cell Survival Using Survivin Inhibitor YM155 is Associated to Oxidative Stress Modulation

Syahrani

Yunita

Wanandi

2020

Asian Pac J Cancer Prev

View full text Add to dashboard Cite

show abstract

The suppression of manganese superoxide dismutase decreased the survival of human glioblastoma multiforme T98G cells

Cited by 11 publications

References 24 publications

Suppression of Manganese Superoxide Dismutase Activity in Rotenone-Treated Human Glioblastoma T98g Cells Reduces Cell Viability

Suppression of Manganese Superoxide Dismutase Activity in Rotenone-Treated Human Glioblastoma T98g Cells Reduces Cell Viability

Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways

Suppression of Rotenone-Treated Human Breast Cancer Stem Cell Survival Using Survivin Inhibitor YM155 is Associated to Oxidative Stress Modulation

Contact Info

Product

Resources

About