Cedrol restricts the growth of colorectal cancer in vitro and in vivo by inducing cell cycle arrest and caspase-dependent apoptotic cell death

Abstract

Background: Cedrol is a natural sesquiterpene alcohol found in Cedrus atlantica, which has been proven to have a broad spectrum of biological activities, such as antimicrobial, anti-inflammatory, analgesic, anxiolytic, and anti-cancer effects. However, the underlying anticancer mechanisms and in vivo inhibitory effects of cedrol on colorectal cancer (CRC) have not been elucidated. In the present study, we investigated the anti-CRC potential of cedrol using in vitro and in vivo models. Methods: The effects of cedrol on cell viability, cell cycle progression, and apoptosis of HT-29 and CT-26 cells were detected by MTT, flow cytometry, and TUNEL assays. Western blotting was used to measure protein expression for molecular signaling analyses. Results: Cedrol inhibited HT-29 and CT-26 cell proliferation in a time-and dose-dependent manner, with IC50 values of 138.91 and 92.46 µM, respectively. Furthermore, cedrol induced cell cycle arrest at the G0/G1 phase by regulating the expression of cell cycle regulators, such as CDK4 and cyclin D1, and triggered apoptosis through extrinsic (FasL/caspase-8) and intrinsic (Bax/caspase-9) pathways. In addition, cedrol in combination with the clinical drug 5-fluorouracil exhibited synergistic inhibitory effects on CRC cell growth. Importantly, cedrol treatment suppressed the progression of CRC and improved the survival rate of animals at a well-tolerated dose. Conclusion: These results suggest that cedrol has an anti-cancer potential via induction of cell cycle arrest and apoptosis, and it could be considered as an effective agent for CRC therapy.