PMID- 35592288 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2048-7177 (Print) IS - 2048-7177 (Electronic) IS - 2048-7177 (Linking) VI - 10 IP - 5 DP - 2022 May TI - Cedrus atlantica extract exerts antiproliferative effect on colorectal cancer through the induction of cell cycle arrest and apoptosis. PG - 1638-1648 LID - 10.1002/fsn3.2786 [doi] AB - Cedrus atlantica is a tree species found in Morocco with many clinical benefits in genitourinary, musculoskeletal, and skin systems. Previous studies have reported that extracts of Cedrus atlantica have antioxidant, antimicrobial, and anticancer properties. However, its role in colorectal cancer (CRC) remains unclear. The present study investigated the effects and underlying mechanisms of Cedrus atlantica extract (CAt) using HT-29 (human colorectal adenocarcinoma) and CT-26 CRC cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure cell viability. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were used to study the cell cycle and cell apoptosis, respectively. The expression of cell cycle and apoptosis-associated proteins was detected by western blotting or immunohistochemical (IHC) staining. CAt showed significant inhibitory effects on the proliferation of HT-29 and CT-26 cells, and combined with the clinical drug, 5-fluorouracil (5-FU), exhibited synergistic effects. CAt induced cell cycle arrest at the G0/G1 phase through the upregulation of p53/p21 and the downregulation of cyclin-dependent kinases (CDKs)/cyclins. In addition, CAt-treated cells exhibited chromatin condensation, DNA fragmentation, and apoptotic bodies, which are typical characteristics of apoptosis activated via both the extrinsic (Fas ligand (FasL)/Fas/caspase-8) and intrinsic (Bax/caspase-9) pathways. Importantly, CAt suppressed tumor progression and prolonged the life span of mice within a well-tolerated dose. Therefore, our findings provide novel insights into the use of CAt for the treatment of CRC. CI - (c) 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC. FAU - Huang, Chih-Yuan AU - Huang CY AUID- ORCID: 0000-0002-7253-6301 AD - Devision of Nephrology Department of Internal Medicine Ditmanson Medical Foundation Chia-Yi Christian Hospital Chia-Yi Taiwan, ROC. RINGGOLD: 71664 AD - Department of Sport Management College of Recreation and Health Management Chia Nan University of Pharmacy and Science Tainan Taiwan, ROC. RINGGOLD: 71664 FAU - Chien, Ju-Huei AU - Chien JH AUID- ORCID: 0000-0003-4971-5616 AD - Department of Research Taichung Tzu-Chi Hospital Buddhist Tzu-Chi Medical Foundation Taichung Taiwan, ROC. AD - Department of Medical Laboratory Science and Biotechnology Central Taiwan University of Science and Technology Taichung Taiwan, ROC. RINGGOLD: 63340 FAU - Chang, Kai-Fu AU - Chang KF AUID- ORCID: 0000-0003-1640-1960 AD - Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 FAU - Hsiao, Chih-Yen AU - Hsiao CY AUID- ORCID: 0000-0003-1199-6977 AD - Devision of Nephrology Department of Internal Medicine Ditmanson Medical Foundation Chia-Yi Christian Hospital Chia-Yi Taiwan, ROC. RINGGOLD: 71664 AD - Department of Hospital and Health Care Administration Chia Nan University of Pharmacy and Science Tainan Taiwan, ROC. RINGGOLD: 71664 FAU - Huang, Ya-Chih AU - Huang YC AD - Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 AD - Institute of Medicine Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 FAU - Chen, Yi-Ting AU - Chen YT AD - Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 FAU - Hsu, Ming-Yi AU - Hsu MY AUID- ORCID: 0000-0003-2778-8638 AD - Department of Nursing Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 AD - Department of Nursing Chung Shan Medical University Hospital Taichung Taiwan, ROC. RINGGOLD: 63276 FAU - Hsieh, Ming-Chang AU - Hsieh MC AD - Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 AD - Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan, ROC. RINGGOLD: 63276 FAU - Tsai, Nu-Man AU - Tsai NM AUID- ORCID: 0000-0002-2629-1833 AD - Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan, ROC. RINGGOLD: 63276 AD - Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan, ROC. RINGGOLD: 63276 AD - Department of Life-and-Death Studies Nanhua University Chiayi Taiwan, ROC. LA - eng PT - Journal Article DEP - 20220221 PL - United States TA - Food Sci Nutr JT - Food science & nutrition JID - 101605473 PMC - PMC9094448 OTO - NOTNLM OT - Cedrus atlantica OT - antiproliferation OT - apoptosis OT - colorectal cancer OT - synergistic inhibition COIS- The authors declare no conflict of interest. EDAT- 2022/05/21 06:00 MHDA- 2022/05/21 06:01 PMCR- 2022/02/21 CRDT- 2022/05/20 02:21 PHST- 2021/10/18 00:00 [received] PHST- 2022/02/01 00:00 [revised] PHST- 2022/02/05 00:00 [accepted] PHST- 2022/05/20 02:21 [entrez] PHST- 2022/05/21 06:00 [pubmed] PHST- 2022/05/21 06:01 [medline] PHST- 2022/02/21 00:00 [pmc-release] AID - FSN32786 [pii] AID - 10.1002/fsn3.2786 [doi] PST - epublish SO - Food Sci Nutr. 2022 Feb 21;10(5):1638-1648. doi: 10.1002/fsn3.2786. eCollection 2022 May.