Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway.
In: Pharmaceuticals (14248247), Jg. 15 (2022-12-01), Heft 12, S. 1589-1605
Online
academicJournal
Zugriff:
Malignant melanoma is the most fatal form of skin cancer worldwide, and earlier diagnosis and more effective therapies are required to improve prognosis. As a possible solution, near-infrared fluorescent heptamethine cyanine dyes have been shown to be useful for tumor diagnosis and treatment. Here, we synthesized a novel theranostic agent, IR-817, a multifunctional bioactive small-molecule that has near-infrared emission, targets mitochondria in cancer cells, and has selective anti-cancer effects. In in vitro experiments, IR-817 preferentially accumulated in melanoma cells through organic anion transporting polypeptide transporters but also selectively inhibited the growth of tumor cells by inducing mitochondrial-dependent intrinsic apoptosis. Mechanistically, IR-817 caused G0/G1 cell cycle arrest by targeting the E2F/Cyclin/CDK pathway. Finally, IR-817 significantly suppressed the growth of xenograft tumors in zebrafish and mice. Immunohistochemical staining and hematoxylin and eosin staining revealed that IR-817 induced apoptosis and inhibited tumor cell proliferation without notable side effects. Therefore, mitochondrial-targeting theranostic agent IR-817 may be promising for accurate tumor diagnosis, real-time monitoring, and safe anti-cancer treatments. [ABSTRACT FROM AUTHOR]
Copyright of Pharmaceuticals (14248247) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway.
|
---|---|
Autor/in / Beteiligte Person: | Sun, Changzhen ; Wang, Jianv ; Xia, Tong ; Sun, Qin ; He, Yijing ; Wang, Hailan ; He, Qizhou ; Liu, Li |
Link: | |
Zeitschrift: | Pharmaceuticals (14248247), Jg. 15 (2022-12-01), Heft 12, S. 1589-1605 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 1424-8247 (print) |
DOI: | 10.3390/ph15121589 |
Schlagwort: |
|
Sonstiges: |
|