scholarly journals Sceptrin, a Marine Natural Compound, Inhibits Cell Motility in a Variety of Cancer Cell Lines

2010 ◽  
Vol 5 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Angel Cipres ◽  
Daniel P. O’Malley ◽  
Ke Li ◽  
Darren Finlay ◽  
Phil S. Baran ◽  
...  
BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Karolin Ebert ◽  
Gwen Zwingenberger ◽  
Elena Barbaria ◽  
Simone Keller ◽  
Corinna Heck ◽  
...  

Abstract Background Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. The molecular mechanisms of action for anti-HER-family drugs in gastric cancer cells are incompletely understood. We compared the molecular effects of trastuzumab and the other HER-family targeting drugs cetuximab and afatinib on phosphoprotein and gene expression level to gain insights into the regulated pathways. Moreover, we intended to identify genes involved in phenotypic effects of anti-HER therapies. Methods A time-resolved analysis of downstream intracellular kinases following EGF, cetuximab, trastuzumab and afatinib treatment was performed by Luminex analysis in the gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87. The changes in gene expression after treatment of the gastric cancer cell lines with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 h were analyzed by RNA sequencing. Significantly enriched pathways and gene ontology terms were identified by functional enrichment analysis. Furthermore, effects of trastuzumab and afatinib on cell motility and apoptosis were analyzed by time-lapse microscopy and western blot for cleaved caspase 3. Results The Luminex analysis of kinase activity revealed no effects of trastuzumab, while alterations of AKT1, MAPK3, MEK1 and p70S6K1 activations were observed under cetuximab and afatinib treatment. On gene expression level, cetuximab mainly affected the signaling pathways, whereas afatinib had an effect on both signaling and cell cycle pathways. In contrast, trastuzumab had little effects on gene expression. Afatinib reduced average speed in MKN1 and MKN7 cells and induced apoptosis in NCI-N87 cells. Following treatment with afatinib, a list of 14 genes that might be involved in the decrease of cell motility and a list of 44 genes that might have a potential role in induction of apoptosis was suggested. The importance of one of these genes (HBEGF) as regulator of motility was confirmed by knockdown experiments. Conclusions Taken together, we described the different molecular effects of trastuzumab, cetuximab and afatinib on kinase activity and gene expression. The phenotypic changes following afatinib treatment were reflected by altered biological functions indicated by overrepresentation of gene ontology terms. The importance of identified genes for cell motility was validated in case of HBEGF.


2021 ◽  
Author(s):  
Suneetha Nunna ◽  
Ying-Pei Huang ◽  
Mahdi Rasa ◽  
Krepelova Anna ◽  
Francesco Annunziata ◽  
...  

Abstract BackgroundColorectal cancer (CRC) is one of the most frequent and lethal cancers in the world. The current medical treatment for CRC primarily includes combination of multiple chemotherapeutic, targeted and/or immunotherapeutic drugs. However, these approaches are still not fully successful and cause numerous and severe side effects for the patient. Therefore, there is an urgent need to discover novel and cancer-selective drugs for CRC treatment. As many other natural compounds, a-Mangostin and Paeonol possess anti-cancer properties, but both of these compounds have low solubility and low membrane permeability.Methodsa-Mangostin and Paeonol derivatives were chemically synthesized to increase cytotoxicity versus cancer cell over non-transformed cells. The anticancer properties of these compounds were investigated on human colon cancer cell lines by employing cell viability, apoptosis and cell-cycle analyses. Transcriptome of cancer cells treated with natural compounds were also analyzed by total RNA-sequencing. Finally, we investigated their effects on human colon organoids derived from healthy and cancerous tissue of the same patient.ResultsWe found the two derivative compounds (a-Mangostin-1 (aMan1) and Paeonol-1 (Pae1)) more efficiently induced cytotoxicity in HCT116, HT-29, and SW48 colorectal cancer cell lines than the parental compounds. Both, aMan1 and Pae1 arrested HCT116 cells in G1 and HT-29 and SW48 cells in G2/M phase of the cell cycle. aMan1 and Pae1 induced selective transcriptional responses in CRC cells involving genes related to metabolic stress and DNA damage response signaling pathways. Both aMan1 and Pae1 induced apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue.ConclusionsOur findings increase the knowledge about natural compound derivatives as anticancer compounds and open new research options on the derivation of lead compounds aimed to the development of novel CRC chemotherapeutic drugs that selectively target cancer, but not healthy cells.


2006 ◽  
Vol 175 (4S) ◽  
pp. 258-258
Author(s):  
Ruth Schwaninger ◽  
Cyrill A. Rentsch ◽  
Antoinette Wetterwald ◽  
Irena Klima ◽  
Gabri Van der Pluijm ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document