Critical appraisal of the potential use of cannabinoids in cancer management

Figures & data

Table 1 A selection of cannabinoid receptor ligands and their specificities

Ligand	Source	Action	Specificity	Ki CB1 (nM)	Ki CB2 (nM)
Δ^Citation9-THC	Plant-derived	Nonspecific agonist	CB1 > CB2	5–80	3–75
Cannabidiol	Plant-derived	Low-to-no receptor affinity
Anandamide (AEA)	Endogenous	Nonspecific agonist	CB1»CB2	61–543	279–1,940
2-arachidonoylglycerol (2-AG)	Endogenous	Nonspecific agonist	CB1 > CB2	58–472	145–1,400
R-(+)-Met-anandamide	Synthetic	Nonspecific agonist	CB1»CB2	18–28	815–868
WIN-55,212-2	Synthetic	Nonspecific agonist	CB1 = CB2	2–123	0.3–16
HU-210	Synthetic	Nonspecific agonist	CB1 = CB2	0.06–0.7	0.2–0.52
JWH-133	Synthetic	Selective agonist	CB2	677	3.4
SR141716	Synthetic	Selective antagonist	CB1	1.8	514
SR144528	Synthetic	Selective antagonist	CB2	50–10,000	0.3–6

Notes:K_i values are reported based on reported values for the in vitro displacement of [³H]CP 55,940 (CB₁)- or [³H]HU 243 (CB₂)-binding sites.

Abbreviation: THC, tetrahydrocannabinol.

Table 2 Intracellular action of cannabinoids

Second messenger	Direct effect	Cellular result
Gi/0	Inhibits adenylate cyclase	Decreased cAMP, inhibition of phosphokinase A (PKA)
Gs	Stimulates adenylate cyclase	Increase cAMP, activation of PKA
Gq	Modulation of Ca^2+ channel	Changes in intracellular Ca^2+
Gi/0	Activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs)	Increase in intracellular K
Gi/0	Modulation of ERK1/2	Modulation of p38 MAPK and JNK pathways thereby regulating cellular proliferation, differentiation, movement and death

Notes: Data from.^19,20,25

Abbreviations: ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; JNK, c-Jun NH(2)-terminal protein kinase; cAMP, cyclic adenosine monophosphate.

Table 3 Cannabinoid action in various cancer cell lines

Cell type/line	Source	Cannabinoid	Effect
ND	Bronchial epithelium	THC	Increased proliferation
ND	Endothelial	THC	Increased proliferation
NCI-H292	Lung	THC	Increased proliferation
Hepa	Hepatoma	THC	Increased proliferation
A549	Lung	THC	Increased proliferation
A549, H460, H358	Lung	CBD	Decreased invasion
LNCaP	Prostate	R-(+)-Met	Increased proliferation
PC-3, LNCaP	Prostate	AEA, R-(+)-Met, THC	Decreased proliferation
LNCaP	Prostate	WIN-55,212-2	Decreased proliferation
MCF-7	Breast	AEA, 2-AG, HU-210	Decreased proliferation
MCF-7, MDA-MB-231, MDA-MB-436	Breast	THC, Met-F-AEA, WIN-55,212-2, JWH-133	Decreased proliferation
4T1	Mouse mammary	THC	Decreased proliferation
TSA-E1	Mouse breast cancer	Met-F-AEA	Decreased proliferation
U87-MG, U373	Glioma	CBD	Decreased proliferation
C6	Rat glioma	THC, JWH-122, WIN-55,212-2	Decreased proliferation
U251, SF-126	Glioblastoma	THC	Decreased proliferation
GBM	Glioblastoma	THC, WIN-55,212-2	Decreased proliferation
	Human astrocytoma	JWH-133	Decreased proliferation
KiMol	K-ras-transformed FRTL-5 thyroid	Met-F-AEA	Decreased proliferation
EL-4	Thymoma/lymphoma	HU-210	Decreased proliferation
PDV-C57	Mouse skin carcinoma	JWH-133, WIN-55,212-2	Decreased proliferation
HUVEC	Umbilical vein	JWH-133	Decreased proliferation

Notes: Data from.^55–58

Abbreviations: ND, not described; THC, tetrahydrocannabinol; CBD, cannabidiol; MCF, Michigan Cancer Foundation; R-(+)-Met, R-(+)-methanandamide; AEA, anandamide; 2-AG, 2-arachidonoylglycerol; Met-F-AEA, Met-fluoro-anandamide; GBM, glioblastoma multiforme; HUVEC, human umbilical vein endothelial cell.

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