Tumor-Selective Cytotoxicity of Nitidine Results from Its Rapid Accumulation into Mitochondria

BioMed Research International
Hironori IwasakiHirosuke Oku

Abstract

We identified a nitidine- (NTD-) accumulating organelle and evaluated the net cytotoxicity of accumulated NTD. To evaluate tumor cell selectivity of the drug, we evaluated its selective cytotoxicity against 39 human cancer cell lines (JFCR39 panel), and the profile was compared with those of known anticancer drugs. Organelle specificity of NTD was visualized using organelle-targeted fluorescent proteins. Real-time analysis of cell growth, proliferation, and cytotoxicity was performed using the xCELLigence system. Selectivity of NTD in the JFCR39 panel was evaluated. Mitochondria-specific accumulation of NTD was observed. Real-time cytotoxicity analysis suggested that the mechanism of NTD-induced cell death is independent of the cell cycle. Short-term treatment indicated that this cytotoxicity only resulted from the accumulation of NTD into the mitochondria. The results from the JFCR39 panel indicated that NTD-mediated cytotoxicity resulted from unique mechanisms compared with those of other known anticancer drugs. These results suggested that the cytotoxicity of NTD is only induced by its accumulation in mitochondria. The drug triggered mitochondrial dysfunction in less than 2 h. Similarity analysis of the selectivity of NTD in...Continue Reading

References

Jan 1, 1988·Annual Review of Cell Biology·L B Chen
Feb 14, 1984·Biochemical and Biophysical Research Communications·J S Modica-NapolitanoJ R Aprille
Aug 1, 1997·Trends in Biotechnology·M P Murphy
May 30, 2001·Advanced Drug Delivery Reviews·J S Modica-Napolitano, J R Aprille
Apr 2, 2005·Nature Reviews. Cancer·Brian J P Huntly, D Gary Gilliland
Aug 27, 2005·Mitochondrion·Josephine S Modica-Napolitano, Keshav K Singh
Feb 9, 2006·Cancer Chemotherapy and Pharmacology·Hironori IwasakiMasashi Inafuku
Aug 19, 2007·Molecular Pharmacology·Noriyuki NakatsuTakao Yamori
Jul 25, 2009·Cancer Chemotherapy and Pharmacology·Hironori IwasakiHirosuke Oku
Mar 20, 2010·Cancer Chemotherapy and Pharmacology·Hironori IwasakiHirosuke Oku
Oct 21, 2010·Cancer Prevention Research·Franziska Michor, Kornelia Polyak
Nov 17, 2010·Journal of Microbiological Methods·H SlaninaA Schubert-Unkmeir
Mar 10, 2011·Nature Medicine·Hans Clevers
Sep 20, 2011·Advances in Cancer Research·Alexander Pietras
Mar 23, 2013·Cancer Cell·Shoichiro TakeishiKeiichi I Nakayama
Jul 17, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Mingjuan SunQifeng Yang

❮ Previous
Next ❯

Citations

Aug 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guojun YanJinhuo Pan

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay

Software Mentioned

COMPARE
ImageJ
SCADS
xCELLigence
Time Cell Analyzer - ( RTCA - )
Real

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.