Tanshinones induce tumor cell apoptosis via directly targeting FHIT

Abstract The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding prot...

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Autores principales:	Xianglian Zhou, Yuting Pan, Yue Wang, Bojun Wang, Yu Yan, Yi Qu, Xisong Ke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9338087c3bd4153b81525e4508586f1
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spelling	oai:doaj.org-article:a9338087c3bd4153b81525e4508586f12021-12-02T17:52:41ZTanshinones induce tumor cell apoptosis via directly targeting FHIT10.1038/s41598-021-91708-z2045-2322https://doaj.org/article/a9338087c3bd4153b81525e4508586f12021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91708-zhttps://doaj.org/toc/2045-2322Abstract The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.Xianglian ZhouYuting PanYue WangBojun WangYu YanYi QuXisong KeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xianglian Zhou Yuting Pan Yue Wang Bojun Wang Yu Yan Yi Qu Xisong Ke Tanshinones induce tumor cell apoptosis via directly targeting FHIT
description	Abstract The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.
format	article
author	Xianglian Zhou Yuting Pan Yue Wang Bojun Wang Yu Yan Yi Qu Xisong Ke
author_facet	Xianglian Zhou Yuting Pan Yue Wang Bojun Wang Yu Yan Yi Qu Xisong Ke
author_sort	Xianglian Zhou
title	Tanshinones induce tumor cell apoptosis via directly targeting FHIT
title_short	Tanshinones induce tumor cell apoptosis via directly targeting FHIT
title_full	Tanshinones induce tumor cell apoptosis via directly targeting FHIT
title_fullStr	Tanshinones induce tumor cell apoptosis via directly targeting FHIT
title_full_unstemmed	Tanshinones induce tumor cell apoptosis via directly targeting FHIT
title_sort	tanshinones induce tumor cell apoptosis via directly targeting fhit
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a9338087c3bd4153b81525e4508586f1
work_keys_str_mv	AT xianglianzhou tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT yutingpan tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT yuewang tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT bojunwang tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT yuyan tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT yiqu tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit AT xisongke tanshinonesinducetumorcellapoptosisviadirectlytargetingfhit
_version_	1718379185309745152

Tanshinones induce tumor cell apoptosis via directly targeting FHIT

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