ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(10):3173-3182. doi:10.7150/jca.94546 This issue Cite
Research Paper
Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination
1. Department of Oral and Maxillofacial Surgery, Changde Hospital, Xiangya School of Medicine, Central South University (The first people's hospital of Changde City), Changde, Hunan 415000, China.
2. Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
# These authors contributed equally to this work.
Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.
Keywords: Oral squamous cell carcinoma, MCL-1, Ubiquitination, FBW7.
Citation styles
