Triggering of Apoptosis in Osteosarcoma 143B Cell Line by Carbon Quantum Dots via the Mitochondrial Apoptotic Signal Pathway

Author:

Jiao Yang1,Guo Yimin2,Fan Yingcong3,Wang Rui1,Li Xiang1,Wu Hao1,Meng Zhichao1,Yang Xin1,Cui Yunpeng1,Liu Heng1,Pan Liping1,Maimaitijuma Talatibaike1,Zhang Jiazhen4,Wang Yahong5,Cao Yongping1ORCID,Zhang Tao26ORCID

Affiliation:

1. Department of Orthopedic Surgery, Peking University First Hospital, Beijing 100034, China

2. School of Materials Science and Engineering, Beihang University, Beijing 100191, China

3. Peking University Cancer Hospital & Institute, Beijing 100142, China

4. School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

5. Harbin Chengcheng Institute for Material and Life, Harbin 150500, China

6. School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China

Abstract

Objectives. Carbon-based nanomaterials have gained attention in the field of biomedicine in recent years, especially for the treatment of complicated diseases such as cancer. Here, we report a novel carbon-based nanomaterial, named carbon quantum dots (CQDs), which has potential for cancer therapy. We performed a systematic study on the effects of CQDs on the osteosarcoma 143B cell line in vitro and in vivo. Methods. Cell counting assay, the neutral red assay, lactic dehydrogenase assay, and fluorescein isothiocyanate (FITC) Annexin V/Propidium iodide (PI) were used to detect the cytotoxicity and apoptosis of CQDs on the 143B cell line. Intracellular reactive oxygen species (ROS) were detected by the oxidation-sensitive fluorescent probe 2,7-dichlorofluorescein diacetate. The JC-10 assay was used to detect the mitochondrial membrane potential (MMP) of 143B cells incubated with CQDs. The effects of CQDs on the 143B cell line were evaluated by Western blot and immunofluorescence analysis of apoptosis-related proteins Bax, Bcl-2, cytochrome-C, caspase-3, cleaved-caspase-3, PARP1, and cleaved-PARP1. Male tumor-bearing BALB/c nude mice were used to investigate the antitumor effects of CQDs, and the biosafety of CQDs in vivo was tested in male BALB/c mice by measuring weight changes, hematology tests, and histological analyses of major organs. Results. CQDs exhibited a high cytotoxicity and induced apoptosis toward the 143B cell line. CQDs can also significantly increase the intracellular level of ROS and lower the mitochondrial membrane potential levels of 143B cells. CQDs increase apoptotic protein expression to induce apoptosis of 143B cells by triggering the mitochondrial apoptotic signaling pathway. The tumor volume in the CQD-treated mice was smaller than that in the control group, the tumor volume inhibition rate was 38.9%, and the inhibitory rate by tumor weight was 30.1%. All biosafety test indexes were within reference ranges, and neither necrosis nor inflammation was observed in major organs. Conclusions. CQDs induced cytotoxicity in the 143B cell line through the mitochondrial apoptotic signaling pathway. CQDs not only showed an antitumor effect but also high biocompatibility in vivo. As a new carbon-based nanomaterial, CQDs usage is a promising method for novel cancer treatments.

Funder

Harbin Chengcheng Institute

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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