Table 1: Effect in vitro of natural and synthetic jasmonates on normal and cancer cells.

Jasmonate(JAs conc range) vehicleCell linesEffectsReferences

JA, MJ 0.5–3.0 mM/EtOHNormal mononuclear cells from blood (healthy donors)No cytotoxicity [15, 38]
Acute human T-lymphoblastic leukemia Molt-4 and
androgen-responsive human prostate adenocarcinoma LNCap
JA 3 mM: 90% cytotoxicity
MJ 0.5 mM: 87.5% cytotoxicity
↑apoptosis (↑caspase-3) ↑necrosis,
PTPC opening, arrest at G0/G1
Human melanoma SK-28JA: proliferation
MJ: ↑cytotoxicity ↑cell death
Human breast carcinoma MCF-7JA: proliferation
MJ: ↑cytotoxicity ↑cell death
Murine lymphoma EL-4MJ: ↑cytotoxicity

MJ3.0 mM
no vehicle reported
Acute human T-lymphoblastic
leukemia Molt-4
↑p38 ↑JNK ↑AP-1, however,
cell death MAPK-independent

JA, CJ, and MJ(mM)Prostate PC-3, HTB-81proliferation [46]

MJ0.0–0.4 mM
no vehicle reported
Human myeloid
leukemia HL-60 cells
cell growth ↑MAPK
↑differentiation to mature cells

MDDHJ (synthetic) 0–250 μM
no vehicle reported
Human myeloid
leukemia HL-60 cells
Monocytoid leukemia
U937, THP-1 cells
Promyelocytic leukemia
NB4 cells
Lung adenocarcinoma
PC9, PC14 cells
MDDHJ more potent than MJ:
cell growth ↑MAPK
↑differentiation to mature cells

MJ0.5–5.0 mMHuman lung adenocarcinoma A549proliferation ↑ROS ↑apoptosis
(↑Bax/Bcl-Xs ↑caspase-3)

JA, CJ, and MJ
0.5–3.0 mM/EtOH
Acute human T-lymphoblastic
leukemia Molt-4 cells
Molt-4: ↑mitochondrial membrane depolarization ↑cyt c release ↑swelling ↑cell death [38]
Lymphocytes from CLL patientsCLL cells: ↑mitochondrial membrane depolarization ↑cytotoxicity
Liver carcinoma Hep 3B cellsHep3B: ↑mitochondrial membrane depolarization (PTPC mediated) ↑cyt c release ↑swelling ↑cell death
Human fibroblast 3T3 cells (nontransformed cell line)
Normal blood   
Nontransformed 3T3 cells: no cytotoxicity
Normal lymphocytes: no cytotoxicity

JA, MJ 0.25–3.0 mM/EtOHB-lymphoma clone
29M6.2 (wild type p53)
B-lymphoma clone
wt p53 cells: ↑apoptosis
mutant p53: ↑nonapoptotic cell death
29M6.10 (mutant p53, resistant to treatment) MJ: ↑~90% ATP depletion in both cell types
2DG, high Glc, but not pyruvate: ATP

CJ, MJ0.5–2.5 mMNonsmall cell lung cancer lines A549 and H520proliferation, cell cycle arrest at G2/M phase ↑p38 and ERK1/2 phosphorylation ↑Bax↑p21 ↑caspase-3 [37]

MJ0.5–2.0 mMHormone-refractory prostate adenocarcinomas PC-3, DU-145 proliferation ↑apoptosis 5-LOX[47]

MJ1–2.6 mM/EtOH—(IC50)Murine melanoma cells
B16F10 and B16 COL/R (overexpressing Pgp, MDR)
cell motility cell growth MDR[39]

TBrJA (synthetic)40 μM/EtOH
(MJ doses lower than in vitro)
Melanoma B16-F10
Breast MCF-7
Pancreas Mia PCA-2
D122, PBL
↑citoxicity (TBrJA ≫ MJ)[39]

MJ0.5–3.0 mM
no vehicle reported
CT-26 (murine colon carcinoma)
B16 (murine melanoma)
BCL1 (murine B-cell leukemia)
Molt-4 (human T-lymphoblastic
leukemia cell line)
MJ (but not JA) detached HK1 and HK2 from VDAC1 in isolated mitochondria from the
four cell lines
MJ did not inhibit HKs activity;
ATP ↑cyt c release ↑mitochondria swelling, ↑cell death
[20, 30]

MJ1.0-2.0 mMHuman neuroblastoma
Arrest at S-phase cell growth
XIAP mRNA survivin mRNA ↑apoptosis

MJ 0.5–3.0 mM/DMSOHuman breast cancer MCF-7
Human melanocytic MDA-MB-435 cells [74]
Arrest at G0/G1and S-phase membrane fluidity ↑apoptosis: extrinsic (TNFR1, ↑caspase-8); intrinsic [Δ ↑caspase-3 (only MDA-MB-435)] [25]

CJ, MJ2.0 mM/DMSOHormone-independent prostate PC-3, DU-145 cells Cell cycle arrest cell growth ↑apoptosis
(↑TNFR1, ↑caspase-3)

JA, CJ, and MJ 1.0-2.0 mM/DMSOHuman neuroblastoma
Arrest at G2/M phase cell growth ↑apoptosis (XIAP survivin) activities: MJ > JA > CJ [44]
Human embryonic kidney HEK 293 cellsNot affected by MJ

MJ1.0-2.0 mM/DMSOHuman neuroblastoma
SK-N-SH, BE(2)-C
Arrest at G0/G1 phase cell viability
mRNA of PCNA ↑apoptosis (XIAP survivin)

MJ0.5–3.0 mM/EtOHSarcomas: MCA-105, ↑pAkt (correlates with lower sensitivity to cytotoxicity by MJ) [49]
SaOS-2 (resistent to MJ)MJ + 2DG: ↑cytotoxicity

MJ1.0–5.0 mM/EtOHCervical cancer SiHA, CaSki, and HeLa cells: having wt p53
Cervical cancer C33A cells (with mutated p53)
cell cycle ↑apoptosis through different pathways
ATP ↑lactate (in more glycolytic CaSki); PARP cleavage, multiple cell death pathways depending on levels of p53, p21, Bcl-2, and Bax

JA, MJ0.25–4.0 mM/EtOHAcute myelogenous leukemia cells
HL-60 and KG1
↑ROS ↑MJ-induced mitochondrial membrane depolarization ↑MJ-induced Mit. SOD AKRC1 [132]

MJ, MDDHJ0.15 mM/DMSOLeukemia HL-60 cells↑Ca2+-binding protein S100P ↑differentiation ↑regulator of G-protein signaling-16 (RGS16) [42]

J7 (synthetic)IC50 15 μMHuman cervical carcinoma
HeLa cells
Cell cycle arrest at G2/M phase, Bcl-2 (caspase 9, 3) DNA damage[27]

J7 (synthetic)50 µM/DMSOHuman hepatoma Hep3B↑Bax/Bcl-2 ratio ↑DR5 ↑caspase-8 Bid ↑apoptosis correlated with: ↑caspase-9 ↑caspase-3 XIAP cIAP PARP. Extrinsic/intrinsic/MAPK[34]

MJ 0.5–2.5 mM
no vehicle reported
CD138+ tumor
cells from MM patients
HK2 release from mitochondria,
rapid ATP ↑apoptosis

MJ0.25–1.0 mM
no vehicle reported
Human colorectal cancer cells CRC↑TRAIL ↑cyt c release
↑caspase cleavage survivin
TCF transcriptional activity

MJ0.0–2.0 mM/EtOHCervical cancer cells
SiHa, CaSki, HeLa, and C33A
↑mitochondrial (HeLa, CaSki)
survivin E6, E7 (HPV)
↑different cell death pathways (independently of HPV)

J7 (synthetic)0–50 μM/ DMSOHuman hepatoma HepG2 ↑ROS ↑TRAIL-mediated apoptosis (Bid XIAP cIAP Bcl-xL ↑caspases)[35]

MJ 3.0 mM (IC50) no vehicle reportedHuman adenocarcinoma colon HT-39  Arrest at S-G2/M ↑cytotoxicity ↑apoptosis [31]

JA, MJ1.0–3.0 mM/DMSOCanine macrophagic malignant DM62 cellscell growth (MJ > JA) ↑cytotoxicity [256]

MJ0.5–0.2 mM/DMSOHuman gastric SGC-7901, MKN-45 cell linesmigration invasion angiogenesis

Bcl-2: B-cell lymphoma-2; Bcl-xL: B-cell lymphoma-extra large. Bid: BH3 interacting domain death agonist; cIAP: cellular inhibitor of apoptosis; CJ: cisjasmonic acid; 2DG: 2-deoxy-D-glucose; Glc: glucose; J7: methyl 5-chloro-4,5-didehydrojasmonate; JA: jasmonic acid; NSCLC: nonsmall-cell lung carcinoma; Pgp: P-glycoprotein; MDDHJ: methyl 4,5-didehydro-jasmonate; MDR: multidrug resistance; MMP-14: matrix metalloprotease 14; PARP: poly (ADP-ribose) polymerase; PCNA: proliferating cell nuclear antigen; PTPC: permeability transition pore complex; ROS: reactive oxygen species; S100P: protein SP100; TBrJA: 5,7,9,10-tetrabromo jasmonate; TNFR1: tumor-necrosis factor receptor-1; TRAIL: tumor necrosis factor- (TNF-) related apoptosis-inducing ligand; XIAP: X-linked inhibitor of apoptosis protein.