bims-aporos 2018-10-07 papers

Issue of 2018–10–07
three papers selected by
Gavin McStay, Staffordshire University

Nanoscale Res Lett. 2018 Sep 29. 13(1): 304

The Apoptosis Effect on Liver Cancer Cells of Gold Nanoparticles Modified with Lithocholic Acid.

Mei-Xia Zhao, Zhong-Chao Cai, Bing-Jie Zhu, Zhi-Qiang Zhang.

Functionalized gold nanoparticles (AuNPs) have widely applied in many fields, due to their good biocompatibility, a long drug half-life, and their bioactivity is related to their size and the modified ligands on their surface. Here, we synthesized the AuNPs capped with ligands that possess polyethylene glycol (PEG) and lithocholic acid (LCA) linked by carboxyl groups (AuNP@MPA-PEG-LCA). Our cytotoxicity results indicated that AuNP@MPA-PEG-LCA have better cell selectivity; in other words, it could inhibit the growth of multiple liver cancer cells more effectively than other cancer cells and normal cells. Apoptosis plays a role in AuNP@MPA-PEG-LCA inhibition cell proliferation, which was convincingly proved by some apoptotic index experiments, such as nuclear staining, annexin V-FITC, mitochondrial membrane potential (MMP) analysis, and AO/EB staining experiments. The most potent AuNP@MPA-PEG-LCA were confirmed to efficiently induce apoptosis through a reactive oxygen species (ROS) mediating mitochondrial dysfunction. And AuNP@MPA-PEG-LCA could be more effective in promoting programmed cell death of liver cancer cells.

Keywords: Apoptosis; Gold nanoparticles; Lithocholic acid; Liver cancer cells

DOI: https://doi.org/10.1186/s11671-018-2653-8

Photodiagnosis Photodyn Ther. 2018 Sep 27. pii: S1572-1000(18)30194-7. [Epub ahead of print]

Apoptosis and autophagy induced by DVDMs-PDT on human esophageal cancer Eca-109 cells.

Yin Shi, Boli Zhang, Xiaolan Feng, Fei Qu, Shuang Wang, Lijie Wu, Xiaobing Wang, Quanhong Liu, Pan Wang, Kun Zhang.

BACKGROUND: Esophageal cancer is a common gastrointestinal cancer. About 300,000 people die from esophageal cancer every year in the world. Photodynamic therapy (PDT) has recently attracted attention as a feasible alternative to cancer therapy. Sinoporphyrin sodium (DVDMs) is a novel sensitizer isolated from photofrin. In this study, we aimed to investigate the effects of DVDMs mediated photodynamic therapy and the possible mechanism on human esophageal cancer Eca-109 cells.
METHODS: Cell viability was measured by MTT assay and cell apoptosis was determined by Annexin V-PE/7-AAD and western blot. MDC staining and western blot were used to evaluate cell autophagy. The production of intracellular reactive oxygen species (ROS) was detected by flow cytometry. The expression of MAPK and HO-1 were detected by western blot.
RESULTS: DVDMs-PDT decreased cell viability and induced cell apoptosis and autophagy. Autophagy inhibition reduced cell apoptosis triggered by DVDMs-PDT in Eca-109 cells. Generation of ROS was detected in DVDMs-PDT group. p38MAPK, JNK and HO-1 were activated after PDT treatment and the activation were reversed by adding ROS scavenger NAC.
CONCLUSIONS: Our studies demonstrated that DVDMs-PDT induced apoptosis and autophagy in Eca-109 cells. DVDMs-PDT induced ROS generation in Eca-109 cells, and the generation of ROS activated p38MAPK and JNK. Activation of p38MAPK and JNK may be involved in PDT-induced apoptosis.

Keywords: DVDMs; Eca-109 cells; Photodynamic therapy; apoptosis; autophagy

DOI: https://doi.org/10.1016/j.pdpdt.2018.09.013

Eur J Pharmacol. 2018 Sep 27. pii: S0014-2999(18)30564-8. [Epub ahead of print]

Targeting EphA4 abrogates intrinsic resistance to chemotherapy in well-differentiated cervical cancer cell line.

Shinichiro Kina, Takao Kinjo, Feixin Liang, Toshiyuki Nakasone, Hideyuki Yamamoto, Akira Arasaki.

Alkylating reagent chemotherapy for human cancers is not curative, and relapse occurs due to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD cells after chemotherapy, a phenomenon referred to as intrinsic resistance, depends on reactive oxygen species. Well-differentiated regions of the tumor are intrinsically resistant to chemotherapy. Receptor tyrosine kinase erythropoietin-producing human hepatocellular receptor A4 (EphA4) protein is highly expressed in the well-differentiated tumor-derived cervical cancer cell line Caski, but not in poorly differentiated tumor-derived cervical cancer cell lines such as HeLa or SiHa. Here, we report that reactive oxygen species produced by cisplatin exposure induce tyrosine phosphorylation of EphA4. After observing that EphA4 is activated by cisplatin, we rationalized a combination chemotherapy that induces well-differentiated cervical cancer death. Pharmacological inhibition of EphA4 increased cisplatin-induced cell death in Caski cells. Moreover, we observed increased expression levels of the senescence marker cyclin-dependent kinase inhibitor 2A (p16) in the absence of EphA4 kinase function after stimulation of Caski cells with cisplatin exposure. Mechanistically, cisplatin induces chemotherapy resistance of Caski cells by upregulating Lyn, a Src family kinase (SFK) that interacts with EphA4, through a pathway involving reactive oxygen species. Thus, the reactive oxygen species-SFK-EphA4 axis presents new potential drug targets for chemotherapy resistance.

Keywords: chemotherapy; erythropoietin-producing human hepatocellular receptor A4 (EphA4); reactive oxygen species; tyrosine phosphorylation; well-differentiated tumor

DOI: https://doi.org/10.1016/j.ejphar.2018.09.031