1. Department of Research, Taichung Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, Taichung 42743, Taiwan, R.O.C.
2. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan, R.O.C.
3. Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
4. Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
5. Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C.
6. Division of Hematology and Oncology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan, R.O.C.
7. Institute of Pharmacology, National Taiwan University, Taipei 10617, Taiwan, R.O.C.
8. Division of Hematology‑Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan, R.O.C.
9. Min-Hwei Junior College of Health Care Management, Tainan 73658, Taiwan, R.O.C.
10. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C.
11. Department of Life-and-Death Studies, Nanhua University, Chiayi 62249, Taiwan, R.O.C.
#These authors contributed equally to this work.
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.
Keywords: Cedrol, colorectal cancer, cell cycle arrest, apoptosis, synergistic effect