Towards the Small and the Beautiful: A Small Dibromotyrosine Derivative from Pseudoceratina sp. Sponge Exhibits Potent Apoptotic Effect through Targeting IKK/NFκB Signaling Pathway

@article{Su2013TowardsTS,
  title={Towards the Small and the Beautiful: A Small Dibromotyrosine Derivative from Pseudoceratina sp. Sponge Exhibits Potent Apoptotic Effect through Targeting IKK/NF$\kappa$B Signaling Pathway},
  author={Jui Hsin Su and Yu-Cheng Chen and Mohamed El‐Shazly and Ying-Chi Du and Chiang-Wen Su and Chia-Wei Tsao and Li-lian Liu and Yalan Chou and Wen-Been Chang and Yin-Di Su and Michael Yen-Nan Chiang and Yao-Tsung Yeh and Mei-Chin Lu},
  journal={Marine Drugs},
  year={2013},
  volume={11},
  pages={3168 - 3185}
}
A dibromotyrosine derivative, (1′R,5′S,6′S)-2-(3′,5′-dibromo-1′,6′-dihydroxy-4′-oxocyclohex-2′-enyl) acetonitrile (DT), was isolated from the sponge Pseudoceratina sp., and was found to exhibit a significant cytotoxic activity against leukemia K562 cells. Despite the large number of the isolated bromotyrosine derivatives, studies focusing on their biological mechanism of action are scarce. In the current study we designed a set of experiments to reveal the underlying mechanism of DT cytotoxic… 

Figures from this paper

Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90
TLDR
The results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities, and the molecular docking analysis suggested that 1 exhibited more binding affinity to N-terminal ATP-binding pocket of HSp90 protein than 17-AAG, a standard Hsp 90 inhibitor.
13-Acetoxysarcocrassolide Exhibits Cytotoxic Activity against Oral Cancer Cells through the Interruption of the Keap1/Nrf2/p62/SQSTM1 Pathway: The Need to Move Beyond Classical Concepts
TLDR
The apoptotic effect of 13-AC was found to be mediated through the interruption of the Keap1/Nrf2/p62/SQSTM1 pathway, suggesting its potential future application as an anticancer agent.
Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities
TLDR
The results suggested that the antileukemic effect of HQ is ROS-mediated mitochondrial apoptosis combined with the inhibitory effect on HDAC and topoisomerase activities.
Cracking the Cytotoxicity Code: Apoptotic Induction of 10-Acetylirciformonin B is Mediated through ROS Generation and Mitochondrial Dysfunction
TLDR
10AB-induced apoptosis is mediated through the overproduction of ROS and the disruption of mitochondrial metabolism, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of 10AB.
Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90
TLDR
Heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells and present heteronemin as an interesting candidate for its future development as an antiprostatic agent.
The Antileukemic and Anti-Prostatic Effect of Aeroplysinin-1 Is Mediated through ROS-Induced Apoptosis via NOX Activation and Inhibition of HIF-1a Activity
TLDR
The findings indicated that aeroplysinin-1 targeted leukemia and prostate cancer cells through multiple pathways, suggesting its potential application as an anti-leukemia and prostate cancers drug lead.
Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo
TLDR
It is found that gukulenin A suppressed tumor growth in A2780-bearing mice and may be a potential therapeutic agent for ovarian cancer.
Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression
TLDR
The cytotoxic effect of heteronemin is associated with oxidative stress and induction of phosphorylated talin expression and the use of ROS scavenger, N-acetyl cysteine (NAC), suppressed both the production of ROS from mitochondria and cell apoptosis that were induced byheteronemin treatment.
Isoaaptamine Induces T-47D Cells Apoptosis and Autophagy via Oxidative Stress
TLDR
The cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress and represents an interesting drug lead in the war against breast cancer.
...
...

References

SHOWING 1-10 OF 59 REFERENCES
5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition
TLDR
The results suggest that 5EPA’s cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death.
The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
TLDR
Evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells is provided and a relevant role of the mitochondria in the apoptogenic activity of this compound is indicated.
Antiparasitic Bromotyrosine Derivatives from the Marine Sponge Verongula rigida
TLDR
Nine bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Verongula rigida and screened for their in vitro activity against three parasitic protozoa: Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi.
Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models.
  • Ying-Chi Du, F. Chang, M. Lu
  • Biology, Chemistry
    Phytomedicine : international journal of phytotherapy and phytopharmacology
  • 2012
Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.
TLDR
A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC50 around 1.8 μM.
Antibiotic and Cytotoxic Activity of Brominated Compounds from the Marine Sponge Verongia aerophoba
TLDR
Analysis of the marine sponge Verongia aerophoba from the Canary Islands afforded eight brominated secondary metabolites including the small molecular weight compounds aeroplysinin-1 and the dienone which showed a significantly higher antibiotic as well as cytotoxic activity than their biogenetic precursors.
The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases.
TLDR
The series has excellent selectivity, both within the IKK family over IKK-epsilon, and across a wide variety of kinase assays, which translates to significant cellular activity in assays of functional and mechanistic relevance.
...
...