Marine-Derived Yaequinolone Derivative CHNQD-02792 Suppresses Colorectal Cancer Cell Proliferation and Induces Apoptosis via MAPK Pathway Modulation DOI Creative Commons
Jiaqi Kang,

Tian-Yi Zhou,

Wenhui Wang

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(4), P. 136 - 136

Published: March 21, 2025

Colorectal cancer is currently the third most common malignancy, and toxic side effects of clinical therapeutic drugs often influence treatment outcomes. Marine-derived quinolone alkaloids exhibit various biological activities are particularly notable for their antitumor properties. Compounds 1–13 were semi-synthesized based on 4′-desmethoxyyaequinolone J1, which a 4-phenyl derivative natural alkaloid yaequinolone J1 was isolated from Penicillium sp. FKI-2140. This study first to investigate activity in colorectal cells through proliferation, clonality, apoptosis, cell cycle, MAPK signaling pathway. Cytotoxicity screening against seven lines revealed that CHNQD-02792 (13) had sensitivity HT-29 (IC50 = 4.5 μM), far exceeding positive control 5-fluorouracil 15.58 μM). The plate cloning assay completely inhibited growth at concentration 9 μM. (4.5 μM) CDK1 expression triggered G2/M phase arrest cells. Mechanistic analysis induced apoptosis by suppressing anti-apoptotic protein Bcl-2 upregulating pro-apoptotic proteins Caspase-3 Bax. Furthermore, ERK JNK phosphorylation thus highlighted its regulatory role signaling. These findings suggest exerts cytotoxic via dual mechanisms: inducing while regulating ERK/JNK dephosphorylation. demonstrates targeting tumor proliferation survival pathways, providing foundation further development anti-colorectal drugs.

Language: Английский

Marine-Derived Yaequinolone Derivative CHNQD-02792 Suppresses Colorectal Cancer Cell Proliferation and Induces Apoptosis via MAPK Pathway Modulation DOI Creative Commons
Jiaqi Kang,

Tian-Yi Zhou,

Wenhui Wang

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(4), P. 136 - 136

Published: March 21, 2025

Colorectal cancer is currently the third most common malignancy, and toxic side effects of clinical therapeutic drugs often influence treatment outcomes. Marine-derived quinolone alkaloids exhibit various biological activities are particularly notable for their antitumor properties. Compounds 1–13 were semi-synthesized based on 4′-desmethoxyyaequinolone J1, which a 4-phenyl derivative natural alkaloid yaequinolone J1 was isolated from Penicillium sp. FKI-2140. This study first to investigate activity in colorectal cells through proliferation, clonality, apoptosis, cell cycle, MAPK signaling pathway. Cytotoxicity screening against seven lines revealed that CHNQD-02792 (13) had sensitivity HT-29 (IC50 = 4.5 μM), far exceeding positive control 5-fluorouracil 15.58 μM). The plate cloning assay completely inhibited growth at concentration 9 μM. (4.5 μM) CDK1 expression triggered G2/M phase arrest cells. Mechanistic analysis induced apoptosis by suppressing anti-apoptotic protein Bcl-2 upregulating pro-apoptotic proteins Caspase-3 Bax. Furthermore, ERK JNK phosphorylation thus highlighted its regulatory role signaling. These findings suggest exerts cytotoxic via dual mechanisms: inducing while regulating ERK/JNK dephosphorylation. demonstrates targeting tumor proliferation survival pathways, providing foundation further development anti-colorectal drugs.

Language: Английский

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