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ACKR3 Degradation by the Novel Scutellarein Derivative TBS6b Potently Suppresses Hepatocellular Carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. Scutellarein, derived from the traditional Chinese herb Scutellaria baicalensis, has shown potential against HCC, albeit with limited efficacy. To enhance its therapeutic potential, we synthesized a novel scutellarein derivative, TBS6b, incorporating the antitumor active moieties trimethoxyphenyl and benzimidazole. TBS6b exhibited significantly enhanced anti-HCC activity, surpassing its precursor in both in vitro and in vivo models. Comprehensive assays, including colony formation, EdU incorporation, wound healing, and Transwell migration, demonstrated TBS6b's potent inhibition of HCC proliferation, migration, and invasion. Notably, TBS6b's mechanism of action was elucidated as promoting the ubiquitination and subsequent degradation of the atypical chemokine receptor 3 (ACKR3), a key regulator of HCC's aggressive behavior. Rescue experiments further confirmed that ACKR3 downregulation is central to TBS6b’s anti-cancer efficacy. This study not only identifies ACKR3 as a novel therapeutic target in HCC but also introduces TBS6b as a promising candidate for HCC treatment, offering a new avenue for therapeutic intervention in this lethal disease.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

DISEASE(S): Carcinoma

SUBMITTER: Xiaonan Yang

LAB HEAD: Xiaonan Yang

PROVIDER: PXD053819 | Pride | 2024-08-16

REPOSITORIES: Pride

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			Action	DRS
	Result.zip	Other
	TEclipse_FAIMS_TMT_F1.raw	Raw
	TEclipse_FAIMS_TMT_F10.raw	Raw
	TEclipse_FAIMS_TMT_F2.raw	Raw
	TEclipse_FAIMS_TMT_F3.raw	Raw

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