Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway

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,...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-12, Vol.15 (12), p.1589
Main Authors: Sun, Changzhen, Wang, Jianv, Xia, Tong, Sun, Qin, He, Yijing, Wang, Hailan, He, Qizhou, Liu, Li
Format: Article
Language:English
Subjects:
Antimitotic agents
Antineoplastic agents
Apoptosis
Cancer therapies
Care and treatment
Cell cycle
cell cycle arrest
Diagnosis
Dosage and administration
Drug targeting
Dyes
Evaluation
Health aspects
heptamethine cyanine dyes
Liver
malignant melanoma
Medical prognosis
Melanoma
Metabolism
Methods
Mitochondria
near-infrared imaging
Permeability
Physiological aspects
Skin cancer
Testing
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Summary: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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15121589