المؤلفون: Xu Chen, Jing Yang, Xiaoshan Jiang, Lanzhen Huang, Ang Li, Fei-Cheng Yang, Guanzhen Liao

المصدر: Oncology Letters. 14:1080-1088

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, biology, Cell growth, Articles, Cell cycle, Gene mutation, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, biology.protein, Cancer research, p53 upregulated modulator of apoptosis, Propidium iodide, Viability assay, DAPI

الوصف: Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor-negative and Her-2-negative) is often accompanied by a higher frequency of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of biological targets and a poor sensitivity to conventional therapies. Curcumol is a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a Chinese medicinal herb traditionally used as a cancer remedy. Previous studies have revealed that curcumol is able to block proliferation in various human tumor cell lines. However, the underlying mechanisms have yet to be elucidated. The present study aimed to investigate the anticancer effects of curcumol in the human p53 mutant TNBC MDA-MB-231 cell line and its underlying mechanisms. Cell viability and growth were determined by MTT and a mice xenograft model assay, respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis was evaluated by apoptotic morphology analysis with DAPI staining and flow cytometric analysis following Annexin V/propidium iodide staining. The protein expression in cells was evaluated by immunoblotting. Treatment of MDA-MB-231 cells with curcumol resulted in a significant inhibition of cell proliferation in vitro [half maximal inhibitory concentration (IC50)=240.7±85.0 µg/ml for 48 h and IC50=100.2±13.5 µg/ml for 72 h]. Curcumol treatment also resulted in the suppression of xenograft growth in vivo (100 or 200 µg/kg for 21 days), as well as G1 phase arrest and an apoptotic response, which were accompanied by the upregulation of p73 expression and the activation of the expression of p53 upregulated modulator of apoptosis (PUMA) and Bcl-2 antagonistic killer (Bak). No cleavage of poly (ADP-ribose) polymerase was detected. To the best of our knowledge, the present data demonstrate for the first time that curcumol inhibits the growth of MDA-MB-231 cells and triggers p53-independent apoptosis, which may be mediated by the p73-PUMA/Bak signaling pathway. Curcumol may, therefore, be a potential compound for use in the development of novel TNBC therapeutics.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6dcf49f08326f8d8a6dda7d143b22d6Test
https://doi.org/10.3892/ol.2017.6273Test

المؤلفون: LANZHEN HUANG, ANG LI, GUANZHEN LIAO, FEICHENG YANG, JING YANG, XIAOSHAN JIANG, XU CHEN

المصدر: Oncology Letters; Jul2017, Vol. 14 Issue 1, p1080-1088, 9p, 1 Chart, 4 Graphs

مصطلحات موضوعية: TRIPLE-negative breast cancer, P53 antioncogene, TUMORS, CELL lines, APOPTOSIS, PROTEIN expression

مستخلص: Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor‑negative and Her‑2‑negative) is often accompanied by a higher frequency of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of biological targets and a poor sensitivity to conventional therapies. Curcumol is a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a Chinese medicinal herb traditionally used as a cancer remedy. Previous studies have revealed that curcumol is able to block proliferation in various human tumor cell lines. However, the underlying mechanisms have yet to be elucidated. The present study aimed to investigate the anticancer effects of curcumol in the human p53 mutant TNBC MDA‑MB‑231 cell line and its underlying mechanisms. Cell viability and growth were determined by MTT and a mice xenograft model assay, respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis was evaluated by apoptotic morphology analysis with DAPI staining and flow cytometric analysis following Annexin V/propi­dium iodide staining. The protein expression in cells was eva­luated by immunoblotting. Treatment of MDA‑MB‑231 cells with curcumol resulted in a significant inhibition of cell proliferation in vitro [half maximal inhibitory concentration (IC50)=240.7±85.0 µg/ml for 48 h and IC50=100.2±13.5 µg/ml for 72 h]. Curcumol treatment also resulted in the suppression of xenograft growth in vivo (100 or 200 µg/kg for 21 days), as well as G1 phase arrest and an apoptotic response, which were accompanied by the upregulation of p73 expression and the activation of the expression of p53 upregulated modulator of apoptosis (PUMA) and Bcl‑2 antagonistic killer (Bak). No cleavage of poly (ADP‑ribose) polymerase was detected. To the best of our knowledge, the present data demonstrate for the first time that curcumol inhibits the growth of MDA‑MB‑231 cells and triggers p53‑independent apoptosis, which may be media­ted by the p73‑PUMA/Bak signaling pathway. Curcumol may, therefore, be a potential compound for use in the development of novel TNBC therapeutics. [ABSTRACT FROM AUTHOR]

: Copyright of Oncology Letters is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)