The tumoricidal strategies and mechanisms of the cytotoxic protein–lipid complexes.

Protein–lipid complex	Strategies	Effects on tumor cells	Ref.
HAMLET	Apoptotic action	Enhances p53-independent apoptotic pathway or induces apoptotic-like cell death	18, 60 and 80
	Autophagy process	Enhances a macroautophagic mechanism	80 and 100
	Chromatin structure perturbation	Accumulates in the nuclei of tumor cells and interacts with histones, independent of the histone tail, leading to perturbation of chromatin structure and enhancing cell detachment	60, 66 and 92
	Cell detachment	Induces chromatin condensation through caspase-dependent and -independent stimulation	1 and 4
		Effects chromatin acetylation and exerts activity in synergy with histone deacetylase inhibitors
		Binds to α-actinin and stimulates tumor cell detachment
	Proteasome inhibition	Binds to 20S proteasome core, triggering conformational modifications and enhancing inhibition of its activity	44, 64, 93 and 94
	Apoptosis-promoting p38 pathway	Showed to be the top-scoring cell death mechanism	104
	Ribosome interactions	Interferes with individual ribosomes and intact ribosome proteins
	c-Myc oncogene status	Increased expression of c-Myc oncogene enhances tumor cell death	65
BAMLET	Apoptotic action	Induces tumor cell death according to type of tumor cells	148
	Lysosomal mechanism	Triggers a caspase-independent lysosomal mechanism in tumor cells causing lysosomal membrane perturbation	84
Equine lysozyme–OA complex	Cellular membrane perturbation	Significant structural alterations upon interaction with lipid membranes	76
Bovine LF–OA complex	Apoptotic action	Induces apoptosis through both mitochondrial-mediated and death receptor pathways	12
CAMLET	Cell cycle arrest	Inhibits tyrosine kinase activity	7
	Apoptotic action	Inhibits tyrosine kinase activity and disrupts tumor cell signaling pathways	7
Albumin–OA complex	Cell cycle arrest	Causes induction of cell cycle arrest in a dose-dependent manner	13
	Loss of membrane integrity	Causes increase in the OA exposure, which leads to modification of the selective permeability of the cellular membrane	13
Bovine lactoglobulin–OA complex	Apoptotic action	Induces cell death mechanisms analogous to those of HAMLET	149
Pike pervalbumin–OA complex	Apoptotic action	Induces cell death mechanisms similar to those of HAMLET	150
Lactoglobulin–linoleic acid complex	Apoptotic action	Induces cell death mechanisms similar to those of HAMLET	151
rRecombinant His-tagged HAMLET	Apoptotic action	Activation of caspase-8 dependent on the autophagy-related proteins	152