Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells.

Abstract

BACKGROUND:

Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated.

METHODS:

HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR. Automated quantification of 160 cytoplasm and mitochondrial parameter was done by fluorescence microscopy using CellProfiler software.

RESULTS:

Proteomics identified 21 significant different proteins, which belonged to protein folding/synthesis and cell structure amongst others. Increase of VDAC1 protein responsible for formation of mitochondrial channels was confirmed by mRNA expression. A 10-fold decrease of cytoskeleton proteins (STMN1, TBCA) provided a link to alterations of the cell cycle. CCNB1 and CCNE mRNA were decreased two-fold, and P21CIP increased 10-fold, indicative of cell cycle arrest. Morphological analysis of mitochondrial parameter confirmed a reduced mitochondrial activity.

CONCLUSION:

Hierridin B is a potential anticancer compound that targets mitochondrial activity and function.

• Authors: Sara Freitas, Rosário Martins, Margarida Costa, Pedro N Leão, Rui Vitorino, Vitor Vasconcelos, Ralph Urbatzka
• Journal: Marine drugs (Mar Drugs) Vol. 14 Issue 9 (Aug 31 2016) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 27589771 (Publication Type: Journal Article)

Chemical References

• Anisoles
• Antimetabolites, Antineoplastic
• Apoptosis Regulatory Proteins
• RNA, Messenger
• VDAC1 protein, human
• hierridin B
• Voltage-Dependent Anion Channel 1

Topics

• Anisoles (isolation & purification, pharmacology)
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis Regulatory Proteins (biosynthesis, genetics)
• Cyanobacteria (chemistry)
• Cytoplasm (drug effects, metabolism)
• Genes, cdc (drug effects)
• HT29 Cells
• Humans
• Mitochondria (drug effects, metabolism)
• Models, Molecular
• Protein Folding (drug effects)
• Proteomics
• RNA, Messenger (biosynthesis, genetics)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Voltage-Dependent Anion Channel 1 (drug effects)