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A novel antitumor compound nobiliside D isolated from sea cucumber (Holothuria nobilis Selenka).

ABSTRACT: An anticancer compound, triterpene glycoside, was isolated from Holothuria nobilis Selenka. Its chemical structure and configuration were determined by two-dimensional nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The novel active compound was identified as nobiliside D, with the molecular formula C40H61O17SNa and chemical name 3-O-[-β-D-pyranosyl (1-2)-4'-O-sulfon-ate-β-D-xylopyranosyl]-alkoxy-9-ene-3β, 12α, 17α, 25β-4 alcohol. An antitumor test was performed using xCELLigence Real-Time Cell Analysis. Nobiliside D exhibited inhibitory effects on human leukemic cell line K562, human leukemia cell line U937, human lung cancer cell line A-549, human cervix carcinoma cell line HeLa, human breast cancer cell line MCF-7 and human liver carcinoma cell line HepG2. Nobiliside exhibited the greatest inhibitory effect on K562 and MCF-7 cells with an IC50 of 0.83±0.14 and 0.82±0.11 µg/ml, respectively. When human tumor cell lines K562 and MCF-7 were treated by nobiliside D (0.5 µg/ml) for 24 h, 45.8% of K562 cells and 58.7% of MCF-7 cells were apoptotic, whereas only 0.5% of un-treated control cells were apoptotic. These data indicate the compound should offer potential as a novel drug for the treatment of a range of cancers.

SUBMITTER: Zhang JJ

PROVIDER: S-EPMC5525587 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:The Aerobic Scope (AS), which reflects the functional capacity for biological fitness, is a highly relevant proxy to determine thermal tolerance in various taxa. Despite the importance of this method, its implementation is often hindered, due to lacking techniques to accurately measure standard- (SMR) and maximal- (MMR) metabolic rates, especially in sluggish marine invertebrates with low oxygen consumption rates, such as sea cucumbers. In this study the AS concept was modified to define a Temperature-induced Aerobic Scope (TAS), based on metabolic rate changes due to temperature adjustments rather than traditionally used physical activity patterns. Consequentially, temperature dependent peak and bottom O2 consumption rates, defined as Temperature-induced Maximal- (TMMR) and Standard Metabolic Rates (TSMR), respectively, served as MMR and SMR alternatives for the sea cucumber Holothuria scabra. TMMR and TSMR were induced through acute temperature change (2°C per hour; 17-41°C) until critical warm (WTcrit) and cold (CTcrit) temperatures were reached, respectively. In addition, Hsp70 gene expression linked to respiration rates served as synergistic markers to confirm critical threshold temperatures. O2 consumption of H. scabra peaked distinctly at WTcrit of 38°C (TMMR = 33.2 ± 4.7 μgO2 g-1 h-1). A clear metabolic bottom line was reached at CTcrit of 22°C (TSMR = 2.2 ± 1.4 μgO2 g-1 h-1). Within the thermal window of 22-38°C H. scabra sustained positive aerobic capacity, with assumed optimal performance range between 29-31.5°C (13.85-18.7 μgO2 g-1 h-1). Between 39-41°C H. scabra decreased respiration progressively, while gene expression levels of Hsp70 increased significantly at 41°C, indicating prioritization of heat shock response (HSR) and homeostatic disruption. At the cold end (17-22°C) homeostatic disruption was visible through incrementally increasing energetic expenses to fuel basal maintenance costs, but no Hsp70 overexpression occurred. TMMR, TSMR and TAS proved to be reliable metrics, similar to the traditional energetic key parameters MMR, SMR and AS, to determine a specific aerobic performance window for the sluggish bottom dwelling species H. scabra. In addition, the linkage between respiration physiology and molecular defense mechanisms showed valuable analytical synergies in terms of mechanistic prioritization as response to thermal stress. Overall, this study will help to define lethal temperatures for aquaculture and to predict the effects of environmental stress, such as ocean warming, in H. scabra.

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A novel antitumor compound nobiliside D isolated from sea cucumber (Holothuria nobilis Selenka).

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