Cargando…
Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B
A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus liv...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071572/ https://www.ncbi.nlm.nih.gov/pubmed/24879544 http://dx.doi.org/10.3390/md12063203 |
_version_ | 1782322815657050112 |
---|---|
author | Ye, Panpan Shen, Ling Jiang, Wei Ye, Ying Chen, Chen-Tung Arthur Wu, Xiaodan Wang, Kuiwu Wu, Bin |
author_facet | Ye, Panpan Shen, Ling Jiang, Wei Ye, Ying Chen, Chen-Tung Arthur Wu, Xiaodan Wang, Kuiwu Wu, Bin |
author_sort | Ye, Panpan |
collection | PubMed |
description | A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC(50) dose, all cancer cell lines showed a lower Max effect dose and IC(50) dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR. |
format | Online Article Text |
id | pubmed-4071572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-40715722014-06-26 Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B Ye, Panpan Shen, Ling Jiang, Wei Ye, Ying Chen, Chen-Tung Arthur Wu, Xiaodan Wang, Kuiwu Wu, Bin Mar Drugs Article A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC(50) dose, all cancer cell lines showed a lower Max effect dose and IC(50) dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR. MDPI 2014-05-28 /pmc/articles/PMC4071572/ /pubmed/24879544 http://dx.doi.org/10.3390/md12063203 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Ye, Panpan Shen, Ling Jiang, Wei Ye, Ying Chen, Chen-Tung Arthur Wu, Xiaodan Wang, Kuiwu Wu, Bin Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title | Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title_full | Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title_fullStr | Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title_full_unstemmed | Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title_short | Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B |
title_sort | zn-driven discovery of a hydrothermal vent fungal metabolite clavatustide c, and an experimental study of the anti-cancer mechanism of clavatustide b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071572/ https://www.ncbi.nlm.nih.gov/pubmed/24879544 http://dx.doi.org/10.3390/md12063203 |
work_keys_str_mv | AT yepanpan zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT shenling zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT jiangwei zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT yeying zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT chenchentungarthur zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT wuxiaodan zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT wangkuiwu zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb AT wubin zndrivendiscoveryofahydrothermalventfungalmetaboliteclavatustidecandanexperimentalstudyoftheanticancermechanismofclavatustideb |