Vitamin E analogues as a novel group of mitocans: anti-cancer agents that act by targeting mitochondria.
Mitochondria have recently emerged as new and promising targets for cancer prevention and therapy. One of the reasons for this is that mitochondria are instrumental to many types of cell death and often lie downstream from the initial actions of anti-cancer drugs. Unlike the tumour suppressor gene encoding p53 that is notoriously prone to inactivating mutations but whose function is essential for induction of apoptosis by DNA-targeting agents (such as doxorubicin or 5-fluorouracil), mitochondria present targets that are not so compromised by genetic mutation and whose targeting overcomes problems with mutations of upstream targets such as p53. We have recently proposed a novel class of anti-cancer agents, mitocans that exert their anti-cancer activity by destabilising mitochondria, promoting the selective induction of apoptotic death in tumour cells. In this communication, we review recent findings on mitocans and propose a common basis for their mode of action in inducing apoptosis of cancer cells. We use as an example the analogues of vitamin E that are proving to be cancer cell-specific and may soon be developed into efficient anti-cancer drugs.
Neuzil
Jiri
J
Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia. j.neuzil@griffith.edu.au
Dong
Lan-Feng
LF
Ramanathapuram
Lalitha
L
Hahn
Tobias
T
Chladova
Miroslava
M
Wang
Xiu-Fang
XF
Zobalova
Renata
R
Prochazka
Lubomir
L
Gold
Mikhal
M
Freeman
Ruth
R
Turanek
Jaroslav
J
Akporiaye
Emmanuel T
ET
Dyason
Jeffrey C
JC
Ralph
Stephen J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D014810:Vitamin E