TY - JOUR
T1 - Decyl caffeic acid inhibits the proliferation of colorectal cancer cells in an autophagy-dependent manner in vitro and in vivo
AU - Chen, Ching
AU - Kuo, Yueh Hsiung
AU - Lin, Cheng Chieh
AU - Chao, Che Yi
AU - Pai, Man Hui
AU - Chiang, En Pei Isabel
AU - Tang, Feng Yao
N1 - Funding Information:
This research project is supported by the grant of Ministry of Science and Technology (MOST), Taiwan, R.O.C. under the agreements MOST-104-2320- B-039-041-MY3, 107-2320-B-039-008-MY3, MOST 107-2320-B-005 -003 - MY3, 107-2621-M-005-008 -MY3, MOST107-2321-B-005-009, 108-2321-B-005-004, China Medical University (CMU) grant under agreements CMU102-ASIA-23, CMU103-ASIA- 20, CMU103-S-46, CMU104-S-32, and as well as in part by the Ministry of Education (MOE) Taiwan under the Higher Education Sprout Project at NCHU-IDCSA. Any results, conclusions, or implication described in this publication are from the author(s) of this manuscript and do not necessarily reflect the view of the MOST, MOE, Asia University and CMU. The authors thank Prof. Raymond Rodriguez (Department of Molecular and Cellular Biology, University of California, Davis, CA, USA) for helpful comments and discussion during the preparation of this manuscript. The author would also like to thank the Instrumentation Center and Precise Facility Center at China Medical University for providing technical assistance for this study.
Publisher Copyright:
© 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/5
Y1 - 2020/5
N2 - The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.
AB - The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.
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U2 - 10.1371/journal.pone.0232832
DO - 10.1371/journal.pone.0232832
M3 - Article
C2 - 32401800
AN - SCOPUS:85084588072
SN - 1932-6203
VL - 15
JO - PLoS One
JF - PLoS One
IS - 5
M1 - e0232832
ER -
