A thiopyran derivative with low murine toxicity with therapeutic potential on lung cancer acting through a NF-κB mediated apoptosis-to-pyroptosis switch

• Published in: Apoptosis (London) 2019-02, Vol.24 (1-2), p.74-82
• Main Authors: Chen, Liping, Weng, Bixia, Li, Huimin, Wang, Haonan, Li, Qian, Wei, Xiaoyan, Deng, Hui, Wang, Sicen, Jiang, Chengxi, Lin, Renyu, Wu, Jianzhang
• Format: Article
• Language: English
• Subjects: A549 Cells; Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor agents; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biochemistry; Biocompatibility; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; Cell Biology; Cell death; Cell Line, Tumor; Chemotherapy; Curcumin; Female; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; NF-κB protein; Oncology; Pyrans - chemistry; Pyrans - pharmacology; Pyrans - therapeutic use; Pyroptosis; Pyroptosis - drug effects; Pyroptosis - physiology; RAW 264.7 Cells; Side effects; Signal transduction; Signal Transduction - drug effects; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Sulfhydryl Compounds - therapeutic use; Toxicity; Toxicity Tests; Tumors; Virology; Xenograft Model Antitumor Assays
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-018-1499-y

Pyroptosis is a novel manner of cell death that can be mediated by chemotherapy drugs. The awareness of pyroptosis is significantly increasing in the fields of anti-tumor research and chemotherapy drugs. Invoking the occurrence of pyroptosis is an attractive prospect for the treatment of lung cancer. Here, the compound L61H10 was obtained as a thiopyran derivative to compare its activity with curcumin. It was indicated that L61H10 exhibited good anti-tumor activity both in vitro and in vivo via the switch of apoptosis-to-pyroptosis, which was associated with the NF-κB signaling pathway. In addition, L61H10 had no obvious side effects both in vitro and in vivo. In brief, L61H10 is shown to be a potential anti-lung cancer agent and research on its anti-tumor mechanism provides new information for chemotherapy drug research.