Table 2.

Mechanism of action associated with apoptosis induced by different epothilones.

Epothilone	Cell Line	Mechanism	Reference
Epothilone A	Human neuroblastome CHP134 SK-N-SH C3H (ATCC 226 CCL) (wild type p53)	Apoptosis independent of p53.	[61]
Epothilones A and B	SKOV-3 human ovarian cancer.	Antiproliferative capacity of Epo A and Epo B six and five times higher than that of PTX, respectively Time-dependent induction of apoptosis and necrosis Cell death associated with decreased MMP, and ROS production	[55]
Epothilone B	NCI-H460 (H460) Human NSCLC cell lines	Late Activation of Caspases (cleavage of caspase-8)	[50]
Epothilone B	SKOV-3 human ovarian cancer.	Apoptosis induced mainly by the extrinsic pathway Increased cytosolic cytochrome c level after 4 h of treatment Increased intracellular calcium level > 20% after 24 and 48 h of exposure Increased TRAIL expression Activation of caspases-8 and -3 Cleavage of 116 kDa PARP to 25 kDa fragments	[56]
Epothilone B	OV-90 Human ovarian papillary serous adenocarcinoma.	Activation of receptors on the target cell surface Induction of apoptosis through a TRAIL- and caspase 8-dependent pathway (extrinsic pathway) Release of TNF-related apoptosis-inducing ligand (TRAIL) Immediate activation of initiator caspases 8 and 9, leading to the appearance of caspase 3 DNA fragmentation and reduced repair capacity	[58]
Iaxabepilone	Human epithelial ovarian tumor cell line 2008.C13 (cisplatinum-resistant variant)	Cytosolic accumulation of cytochrome C, Smac/DIABLO, and caspase-3-mediated PARP cleavage activity Increased DR4 and DR5 expressions Decreased intracellular levels of XIAP, cIAP and surviving Cytotoxic effects against cisplatin- and paclitaxel-resistant ovarian cancer cells	[60]
Patupilone (EpoB)	SK-N-SH IMR-32 Human neuroblastoma	Increased ROS generation; specifically, from mitochondria, after 2 h of treatment Accumulation of BIM in the mitochondrial compartment (2.4-fold) after only 6 h of treatment	[57]
Utidelone (UTD1)	RKO HCT116 CACO2 SW620 HCT15 (ABCB1 high-expression)	Mitochondrial pathway-dependent apoptosis > paclitaxel and 5-FU, especially in cells with high ABCB1 expression Increased caspase-3 activity and PARP cleavage Reduction of the mitochondrial membrane potential Release of mitochondrial cytochrome C Increased ROS production and activation of c-Jun N-terminal kinase (JNK) kinase Inhibition of tumor growth in a CRC xenograft mode	[54]

MMP: mitochondrial membrane potential, ROS: Reactive Oxygen Species.