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

  • Int J Med Sci. 2022 Oct 31;19(13):1953-1964. doi: 10.7150/ijms.77719.
Ju-Huei Chien  1  2 ,  Kai-Fu Chang  3 ,  Shan-Chih Lee  4  5 ,  Chien-Ju Lee  3 ,  Yi-Ting Chen  3 ,  Hung-Chih Lai  6  7 ,  Yin-Che Lu  8  9 ,  Nu-Man Tsai  3  10  11
Affiliations
  • 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.
PMID: 36438926 DOI: 10.7150/ijms.77719
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.

Keywords
Cedrol; apoptosis; cell cycle arrest; colorectal cancer; synergistic effect.
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