Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways

Wang, Kun; Fu, Xiaoting; Li, Yuan; Hou, Ya‐Jun; Yang, Mo; Sun, Jingyi; Yi, Shuying; Fan, Cundong; Fu, Xin; Zhai, Jing; Sun, Bo

doi:10.1007/s11064-016-1854-8

Cited by 22 publications

(19 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have found that SeC inhibited human glioma cells growth in 48 h mainly by induction of S-phase arrest through triggering ROS-mediated DNA damage 5 . To explore the oxidative status in SeC-induced apoptosis, we subsequently investigated the ROS generation and several oxidative damage markers.…”

Section: Resultsmentioning

confidence: 91%

“…The kinetics course of ROS generation in U251 cells was monitored using a DCFH-DA probe in 2 h. The mitochondrial superoxide anion in living U251 cells was vividly imaged by Mito-SOX, a mitochondria-targeted red probe. The experimental details of the three detective methods were carried out according to our previous report 5 . All experiments were conducted in accordance with the relevant guidelines and regulations of Taishan Medical University.…”

Section: Methodsmentioning

confidence: 99%

“…Chemotherapy as one of the most effective ways for treatment of human glioma remains disappointed because of its high invasiveness, malignance and resistance 2–5 . Hence, searching novel agents with high efficiency and low side effects for combating human glioma is an urgent priority in drug development.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulated evidences have revealed that apoptosis is the major mechanism for anticancer action of Se-containing compounds 7 . Studies reported that Se-containing compounds could inhibit human cancer cells growth in vitro and in vivo by induction of cell apoptosis 5, 10–15 . Importantly, selenium compounds display less cytotoxicity towards human normal cells, indicating the novel selectivity between cancer cells and human normal cells 12 .…”

Section: Introductionmentioning

confidence: 99%

“…Hence, the TrxR has emerged as potential target for anticancer drug design. Selenocystine (SeC) a natural available Se-containing amino acid has been demonstrated effective in inhibiting several cancer cells growth by induction of cell cycle arrest or/and apoptosis through triggering ROS-mediated oxidative damage in our previous studies 5, 11–15 . For instance, SeC can inhibit A549 human lung adenocarcinoma cells growth through inhibition of TrxR activity and TrxR expression in vitro and in vivo 20 .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

Fan

Zhang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.

show abstract

Section: Resultsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

Fan

Zhang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS‐mediated p53 phosphorylation

Wang

Meng

Wang

et al. 2018

Cell Biology International

View full text Add to dashboard Cite

Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.

show abstract

Prospect of natural products in glioma: A novel avenue in glioma management

Kundu

Das

Dhara

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Glioma is one of the most perplexing cancers because of its infiltrating nature, molecular signaling, and location in central nervous system. Blood-brain barrier acts as a natural barrier to the glioma making it difficult to access by conventional chemotherapy. Clinicians are using natural compounds or their derivatives for several diseases including different cancers. However, the feasibility of using natural compounds in glioma is not explored in details. Natural compounds can act over a wide variety of signaling pathways such as survival and metabolic pathways and induce cell death. Some of the natural agents have additional benefits of crossing biological barrierssuch as blood-brain barrier with ease having few or no impact on the surrounding healthy cells. All of these benefits make natural compounds a prospective candidate for the glioma management. This article evaluates the benefits of using natural compounds for glioma therapy and their possible mechanism of actions. We have discussed the natural compounds assessed currently for glioma therapy and proposed a few novel natural compounds with potential antiglioma effect based on their mechanism of action.

show abstract

Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways

Cited by 22 publications

References 38 publications

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS‐mediated p53 phosphorylation

Prospect of natural products in glioma: A novel avenue in glioma management

Contact Info

Product

Resources

About