CHEMICAL RESEARCH IN TOXICOLOGY
·
2018
·
IF 3.432
Wenjing Dong,Bingwei Yang,Yawen Wang,Jia Yuan,Yunqi Fan,Erqun Song,Yang Song
Polybrominated diphenyl ethers (PBDEs) are emerging organic environmental pollutants, which were accused of various toxic effects. Here, we studied the role of a potential PBDEs quinone metabolite, PBDEQ, on cytotoxicity, oxidative DNA damage, and the alterations of signal cascade in HeLa cells. PBDEQ exposure leads to reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) loss, lactate dehydrogenase (LDH) release, increasing terminal transferase-mediated dUTP-biotin nick end labeling (TUNEL) positive foci, and the elevation of apoptosis rate. Furthermore, we showed PBDEQ exposure result in increased DNA migration, micronucleus frequency, and the promotion of 8-OHdG and phosphorylation of histone H2AX (γ-H2AX) levels. Mechanism study indicated that PBDEQ caused poly(ADP-ribose) polymerase 1 (PARP-1) activation and apoptosis-inducing factor (AIF) nuclear translocation. All together, these results confirmed the occurrence of parthanatos-like cell death upon PBDEQ exposure.
研究领域:
毒理学
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细胞生物学
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环境科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2017
·
IF 4.521
Jing Zhang,Li Li,Yueting Peng,Yu Chen,Xiaoying Lv,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Weiwei Wu,Yan Yang,Yu Zhang,Yina Zeng,Zhuoying Liang,Xiling Song,Yadong Huang,Wei Xue,Siming Yu
Recently, enzyme dynamic therapy (EDT) has gained enormous attraction in cancer therapy. However, the efficiency of EDT is still largely restricted by the inefficient delivery efficiency of chloroperoxidase (CPO) and the insufficient hydrogen peroxide (H 2 O 2 ) content in the tumor microenvironment (TME). In the present work, a biodegradable cupper peroxide decorated hollow polydopamine nanocomposite (HPDCP) with surface functionalization of PEGlated tumor targeting peptide RGD (PEG-RGD) was designed for effective CPO delivery. The resultant nanosystem of HPDCP@CPO@PEG-RGD displayed high CPO delivery efficiency to breast tumors without comprising the enzyme activity. Moreover, the nanosystem can dissociate rapidly in acidic TME by supplying substantial H 2 O 2 and simultaneously releasing Cu 2+ and CPO, followed by initiating self-activated cascade reactions. At the one hand, the self-supplied H 2 O 2 greatly enhanced the singlet oxygen ( 1 O 2 ) generation via the CPO-mediated enzyme dynamic reaction. At the other hand, substantial hydroxyl radical (•OH) was produced via the Cu 2+ -driven Fenton reaction for chemodynamic therapy (CDT). Therefore, the anticancer efficiency of EDT was significantly enhanced due to the synergistic EDT/CDT effect. Mechanism study revealed that 1 O 2 /•OH generated by HPDCP@CPO@PEG-RGD synergistically inhibited breast cancer cells by firstly causing severe lipid peroxidation, followed by triggering mitochondria-mediated apoptosis and causing irreversible DNA damage by inhibiting the expression of DNA repair enzyme poly (ADP-ribose) polymerase 1 (PARP-1).
研究领域:
癌症治疗
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纳米技术
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酶工程
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材料科学
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生物化学
✓ 已验证
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 46
·期 3
·1295-1307
·
IF 3.591
Zhi-Gang Yin,Xiong-Wei Liu,Hui-Juan Wang,Min Zhang,Xiong-Li Liu,Ying Zhou
A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs.
研究领域:
药物化学
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肿瘤学
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药学
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细胞生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）