Decyl caffeic acid inhibits the proliferation of colorectal cancer cells in an autophagy-dependent manner in vitro and in vivo
| Autor: | Man Hui Pai, En-Pei Isabel Chiang, Ching Chen, Cheng-Chieh Lin, Che Yi Chao, Yueh-Hsiung Kuo, Feng-Yao Tang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell signaling Cyclin E Cyclin A Synthesis Phase Apoptosis Signal transduction Mice 0302 clinical medicine Medicine and Health Sciences Enzyme assays Cell Cycle and Cell Division Colorimetric assays AKT signaling cascade Bioassays and physiological analysis Multidisciplinary MTT assay biology Cell Death Chemistry Signaling cascades Gene Expression Regulation Neoplastic Oncology Cell Processes 030220 oncology & carcinogenesis Medicine Female Colorectal Neoplasms HT29 Cells Research Article Programmed cell death General Science & Technology Cell Survival Science Autophagic Cell Death Antineoplastic Agents 03 medical and health sciences Caffeic Acids In vivo Cyclins Autophagy Animals Humans Cell Proliferation Colorectal Cancer Cell growth Biology and Life Sciences Cancers and Neoplasms Cell Biology Cell Cycle Checkpoints HCT116 Cells Xenograft Model Antitumor Assays Research and analysis methods 030104 developmental biology Biochemical analysis biology.protein Cancer research |
| Zdroj: | PLoS ONE PloS one, vol 15, iss 5 PLoS ONE, Vol 15, Iss 5, p e0232832 (2020) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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