The different biological effects of TMPyP4 and cisplatin in the inflammatory microenvironment of osteosarcoma are attributed to G‐quadruplex. (23rd July 2021)

• Record Type: Journal Article
• Authors: Chen, Jianqiang; Jin, Xiangxiang; Mei, Yanan; Shen, Zhe; Zhu, Jufan; Shi, Hongyi; Wang, Minshan; Zheng, Xiaohui; Liang, Guang
• Is Part Of: Cell proliferation. Volume 54:Number 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-23
• Subjects: cisplatin -- G‐quadruplex -- inflammatory microenvironment -- osteosarcoma -- TMPyP4; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13101
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objective: Osteosarcoma (OS) is characterized by high levels of the tumour‐associated inflammatory microenvironment. Moreover, in approximately 60% of OS, telomere length is maintained by alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for OS therapeutic treatment and how the OS inflammatory microenvironment influences the anti‐cancer drug effect remains unknown. Here, we examined the biological effects of TMPyP4 and cisplatin in the inflammatory microenvironment of OS cells. Materials and methods: Immunofluorescence in situ hybridization (IF‐FISH) and C‐circle experiments were used to detect the G‐quadruplex and ALT activity. The redox potential of single guanine, G‐quadruplex and G‐quadruplex/TMPyP4 was evaluated by the lowest unoccupied molecular orbital energy (LUMO), zeta potential and cyclic voltammetry. Cell viability, flow cytometry and apoptosis, Western blot, comet assay, adhesion, transwell and scratch experiments were performed to compare the anti‐tumour proliferation and migration effects of TMPyP4 and cisplatin in the inflammatory microenvironment. Results: This study indicated that compared with cisplatin, TMPyP4 could induce the formation of human telomeres and FAK G‐quadruplex in vitro and in vivo, and TMPyP4‐treated OS cells showed fewer extrachromosomal C‐circles and fewer ALT‐associated promyelocytic leukaemia bodies. Consequently, the ALT activity and FAK‐related cell migration were suppressed by TMPyP4. Mechanistically, the formation of G‐quadruplex resulted in both lower redox potential than G within the genome and FAK transcription inhibition, and TMPyP4 could enhance this phenomenon, especially in the inflammatory microenvironment. Conclusions: Our results reveal that TMPyP4 is more suitable for OS treatment than cisplatin. Abstract : Osteosarcoma is one of the most malignant cancers with high mortality rates. TMPyP4, a photosensitizer and G‐quadruplex stabilizer, and cisplatin possess anti‐tumour pharmacological effect on various cancer cells. Up to now, however, there is no literature report on the anti‐osteosarcoma effect of TMPyP4 or cisplatin in the inflammatory microenvironment. In our study, we found that TMPyP4 has better anti‐osteosarcoma effect than cisplatin in the inflammatory environment, and their different biological effects are attributed to G‐quadruplex.