Pyrrolidinium-type fullerene derivative-induced apoptosis by the generation of reactive oxygen species in HL-60 cells

Nishizawa, Chiho; Hashimoto, Noriyuki; Yokoo, Sachiko; Funakoshi‐Tago, Megumi; Kimura, Tadashi; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

doi:10.3109/10715760903273849

Cited by 43 publications

(36 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In physiological studies, the biological effects of water-soluble fullerene derivatives containing several hydrophilic groups are noteworthy because fullerene itself is water-insoluble. Water-soluble fullerene derivatives are known to possess various biological and pharmacological properties, including antioxidant activity and inhibitory effects against human immunodeficiency virus (HIV) proteases and DNA photocleavage [20]–[23]. Mashino et al also demonstrated that pyrrolidinium fullerene derivative 6 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Anti-Influenza Activity of C60 Fullerene Derivatives

et al. 2013

Self Cite

View full text Add to dashboard Cite

The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti-Influenza Activity of C60 Fullerene Derivatives

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…[31] In addition, significant ROS overload can also cause cytochrome C release from mitochondria, which will trigger cell apoptosis. [32] DNA damage, mitochondrial membrane potential and cellular Ca 2+ level were further measured in this study to explore the molecular mechanism of cytological effects induced by HBCDs exposure on L02 cells. After low concentration of HBCDs exposure (10 −13 -10 −7 M), no obvious change in DNA damage or mitochondrial membrane potential was observed compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

The cytological effects of HBCDs on human hepatocyte L02 and the potential molecular mechanism

An¹,

Zou²,

Chen³

et al. 2013

Journal of Environmental Science and Health, Part A

View full text Add to dashboard Cite

The concentration of hexabromocyclododecanes (HBCDs) in the environment media and organism samples are gradually rising with the increase of HBCDs usage. This study is designed to investigate the cytological effects of HBCDs on human hepatocyte L02 and explore the potential molecular mechanism. The results of CCK-8 assay showed that high concentration of HBCDs (>20 μM) significantly suppressed cell survival, while comparatively lower dose of HBCDs (10(-13)-10(-7)M) slightly stimulated cell proliferation (P < 0.05). In the mean time, high concentration HBCDs markedly induced cell apoptosis and DNA damage, accompanying with increase of intracellular Ca(2+)level and decrease of mitochondrial membrane potential (P < 0.05). ROS level induced by low concentration of HBCDs was comparatively lower than that by high concentration of HBCDs. In addition, low concentration HBCDs exposure (10(-13)-10(-7)M) resulted in up-regulation of PCNA protein expression level in a time-dependent manner. However, high concentration HBCDs exposure led to increase of Apaf-1 expression level. In conclusion, loss of mitochondrial membrane potential and activation of Apaf-1 mediated pathway involve the L02 cell apoptosis induced by high concentration HBCDs exposure. However, low concentration HBCDs exposure could stimulate cell proliferation of L02 cells, which might be associated with enhancement of PCNA expression.

show abstract

“…106-113 Pyrrolidinium fullerene derivatives have been shown to induce mitochondrion- and caspase-dependent apoptosis through the generation of ROS in human promyeloleukaemia (HL-60) cells. 114 …”

Section: Anti Cancer Propertiesmentioning

confidence: 99%