Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway

Context: Shikonins, a series of natural occurring naphthoquinones extracted from Arnebia euchroma (Royle) Jonst. (Boraginaceae), have antitumor activities and low toxicity. Objective: To illuminate potential activity and mechanism of shikonins against colorectal cancer (CRC). Materials and methods:...

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Autores principales:	Yuzhen Zhu, Yu Zhong, Xun Long, Zhu Zhu, Yu Zhou, Hua Ye, Xiaobin Zeng, Xuebao Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	shikonin apoptosis proliferation cell cycle Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cde1ce3a5a4042c9af2856ceb8b1a6e3
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spelling	oai:doaj.org-article:cde1ce3a5a4042c9af2856ceb8b1a6e32021-11-17T14:21:56ZDeoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway1388-02091744-511610.1080/13880209.2019.1626447https://doaj.org/article/cde1ce3a5a4042c9af2856ceb8b1a6e32019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1626447https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Shikonins, a series of natural occurring naphthoquinones extracted from Arnebia euchroma (Royle) Jonst. (Boraginaceae), have antitumor activities and low toxicity. Objective: To illuminate potential activity and mechanism of shikonins against colorectal cancer (CRC). Materials and methods: Five shikonins were isolated from A. euchroma, and elucidated by extensive spectroscopic analysis. Anti-proliferative activities of shikonins (0–100 μg/mL) on human colorectal cells were evaluated by MTT and CCK-8 for 24 or 48 h. Cell apoptosis and cycle distribution were examined by FCM analysis. The expression of PI3K/Akt/mTOR pathway mRNAs and proteins was analysed by RT-PCR and Western blot, respectively. Cell viability, cell apoptosis, cell cycle and protein expression were measured, when co-treated with PI3K/Akt/mTOR pathway inhibitors. The in vivo activity of deoxyshikonin was evaluated using xenograft tumour model. Results: Deoxyshikonin and another four shikonins were isolated and identified. Deoxyshikonin exhibited anti-proliferative activity with IC50 of 10.97 μM against HT29 cells. Moreover, the percentage of early apoptotic cells and G0/G1 cells increased from 1 to 29% and 44 to 67% with 0–50 μg/mL deoxyshikonin, respectively. Deoxyshikonin also down-regulated the expression of PI3K, p-PI3K, Akt, p-Akt308 and mTOR proteins in HT29 and DLD-1 cells. Moreover, LY294002, NVP-BEZ235 and MK-2206 can make deoxyshikonin more cell proliferation inhibited, cell cycle arrested at G0/G1 and apoptosis promoted. In vivo study, the weight of tumour tissues at deoxyshikonin groups was significantly reduced compared with the control group, and PI3K, p-PI3K, Akt, p-Akt308 and mTOR expression was decreased. Discussion and conclusions: We can conclude that deoxyshikonin isolated from Arnebia euchroma inhibited CRC through the PI3K/Akt/mTOR pathway.Yuzhen ZhuYu ZhongXun LongZhu ZhuYu ZhouHua YeXiaobin ZengXuebao ZhengTaylor & Francis Grouparticleshikoninapoptosisproliferationcell cycleTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 412-423 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	shikonin apoptosis proliferation cell cycle Therapeutics. Pharmacology RM1-950
spellingShingle	shikonin apoptosis proliferation cell cycle Therapeutics. Pharmacology RM1-950 Yuzhen Zhu Yu Zhong Xun Long Zhu Zhu Yu Zhou Hua Ye Xiaobin Zeng Xuebao Zheng Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
description	Context: Shikonins, a series of natural occurring naphthoquinones extracted from Arnebia euchroma (Royle) Jonst. (Boraginaceae), have antitumor activities and low toxicity. Objective: To illuminate potential activity and mechanism of shikonins against colorectal cancer (CRC). Materials and methods: Five shikonins were isolated from A. euchroma, and elucidated by extensive spectroscopic analysis. Anti-proliferative activities of shikonins (0–100 μg/mL) on human colorectal cells were evaluated by MTT and CCK-8 for 24 or 48 h. Cell apoptosis and cycle distribution were examined by FCM analysis. The expression of PI3K/Akt/mTOR pathway mRNAs and proteins was analysed by RT-PCR and Western blot, respectively. Cell viability, cell apoptosis, cell cycle and protein expression were measured, when co-treated with PI3K/Akt/mTOR pathway inhibitors. The in vivo activity of deoxyshikonin was evaluated using xenograft tumour model. Results: Deoxyshikonin and another four shikonins were isolated and identified. Deoxyshikonin exhibited anti-proliferative activity with IC50 of 10.97 μM against HT29 cells. Moreover, the percentage of early apoptotic cells and G0/G1 cells increased from 1 to 29% and 44 to 67% with 0–50 μg/mL deoxyshikonin, respectively. Deoxyshikonin also down-regulated the expression of PI3K, p-PI3K, Akt, p-Akt308 and mTOR proteins in HT29 and DLD-1 cells. Moreover, LY294002, NVP-BEZ235 and MK-2206 can make deoxyshikonin more cell proliferation inhibited, cell cycle arrested at G0/G1 and apoptosis promoted. In vivo study, the weight of tumour tissues at deoxyshikonin groups was significantly reduced compared with the control group, and PI3K, p-PI3K, Akt, p-Akt308 and mTOR expression was decreased. Discussion and conclusions: We can conclude that deoxyshikonin isolated from Arnebia euchroma inhibited CRC through the PI3K/Akt/mTOR pathway.
format	article
author	Yuzhen Zhu Yu Zhong Xun Long Zhu Zhu Yu Zhou Hua Ye Xiaobin Zeng Xuebao Zheng
author_facet	Yuzhen Zhu Yu Zhong Xun Long Zhu Zhu Yu Zhou Hua Ye Xiaobin Zeng Xuebao Zheng
author_sort	Yuzhen Zhu
title	Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
title_short	Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
title_full	Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
title_fullStr	Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
title_full_unstemmed	Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway
title_sort	deoxyshikonin isolated from arnebia euchroma inhibits colorectal cancer by down-regulating the pi3k/akt/mtor pathway
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/cde1ce3a5a4042c9af2856ceb8b1a6e3
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Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway

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