Cardiotoxin III (CTX III, also known as cytotoxin 3) is a sixty amino-acid
polypeptidetoxin from the Taiwan cobra Naja atra. CTX III is highly basic and hydrophobic protein.[1] It is an example of a group of snake
cardio/
cytotoxins (
InterPro: IPR003572), which are made up of shorter
snake venomthree-finger toxins. Over 50 different cytotoxin polypeptides have been isolated and sequenced from venom samples. The difference in the CTX functionality may be due to the relatively small difference in the polypeptide's structure, allowing different CTXs to induce lysis in different cell types.[2] The CTX III molecule contains multiple binding sites and is cytolytic for
myocardial cells and human leukemic T cells.[3]
CTX III's molecular structure displays a folding of the polypeptide backbone that creates five stands from a globular structure. These strands form a double and a triple
antiparallel β-sheet.[4] Studies performed with an antibody complementary of CTX III seemed to conclude that the active site for the molecule's hemolytic and cytotoxic functions and characteristics result from two separate sites.
Biological research
Recent evidence has shown that CTX III may induce
apoptosis in
K562 cells via the release of
cytochrome c. Results indicate that the mechanism utilized by CTX III was a
ROS-independent mitochondrial dysfunction pathway. Evidence from a Taiwanese study of CTX III suggest that the polypeptide selectively enhances
apoptosis induction in
CD8+ T cells.[5] Another study performed using
MDA-MB-231 breast cancer cells concluded that CTX III could induce apoptosis via concomitant inactivation of the
JAK2,
STAT3,
PI3K, and
Akt signaling pathways.[6] In Colo205, human colorectal cancer cells, CTX III was found to induce apoptosis. HepG2, a type of carcinoma cell found in humans, was found to undergo apoptosis through S phase arrest when exposed to isolated toxin samples.[7] The toxin's membrane disturbing activity was found not necessary in inducing cell death in a study using
U937 cells via the Ca2+/PP2A/AMPK axis.[8]