Related Experiment Video
Updated: Sep 15, 2025

SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Casticin activates Rheb GTPase by binding to residue Trp141 and induces tumor senescence
Tao Su1, Zhiqiang Shi2, Jincheng Tan2
1State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Chinese Medicine Guangdong Laboratory, Hengqin, Guangdong, China.
None:
Senescence is a state of irreversible growth arrest that can be induced in colorectal cancer (CRC). Developing drugs that can induce senescent CRC cells without promoting stemness can significantly improve treatment outcomes. Our study reveals a unique mechanism by which casticin (CAS) induces senescence in CRC. Importantly, CAS treatment does not induce stemness in CRC, as demonstrated both in vitro and in vivo. Further investigations showed that CAS binds to Rheb protein at residue Trp141, changing the conformation of Rheb protein, increasing its protein stability and activity. Additionally, CAS elevates AMPK activity. Knockdown of Rheb suppresses AMPK activity, indicating that AMPK acts downstream of Rheb. Crucially, inhibiting either Rheb or AMPK completely abolishes CAS-induced senescence in CRC. This study demonstrates that CAS binding to Trp141 activates Rheb GTPase, effectively inducing senescence in CRC through the Rheb/AMPK signaling pathway without promoting cancer cell stemness. This novel discovery highlights the potential for developing herbal-based senescence-inducing agents targeting Rheb for cancer treatments.
More Related Videos
08:48An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
The Ras Gene
Ras is a...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
MAPK Signaling Cascades