Jasmonate (JAs conc range) vehicle Cell lines Effects References
JA, MJ
0.5–3.0 mM/EtOH Normal 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-28 JA: ↓ proliferation MJ: ↑cytotoxicity ↑cell death Human breast carcinoma MCF-7 JA: ↓ proliferation MJ: ↑cytotoxicity ↑cell death Murine lymphoma EL-4 MJ: ↑cytotoxicity MJ 3.0 mM no vehicle reported Acute human T-lymphoblastic leukemia Molt-4 ↑p38 ↑JNK ↑AP-1, however, cell death MAPK-independent [18 ] JA, CJ, and MJ (mM) Prostate PC-3, HTB-81 ↓ proliferation [46 ] MJ 0.0–0.4 mM no vehicle reported Human myeloid leukemia HL-60 cells ↓ cell growth ↑MAPK ↑differentiation to mature cells[41 ] MDDHJ (synthetic) 0–250 μ M 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 [41 ] MJ 0.5–5.0 mM Human lung adenocarcinoma A549 ↓ proliferation ↑ROS ↑apoptosis (↑Bax/Bcl-Xs ↑caspase-3)[36 ]
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 patients CLL cells: ↑mitochondrial membrane depolarization ↑cytotoxicity Liver carcinoma Hep 3B cells Hep3B: ↑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/EtOH B-lymphoma clone 29M6.2 (wild type p53) B-lymphoma clone wt p53 cells: ↑apoptosis mutant p53: ↑nonapoptotic cell death
[17 ] 29M6.10 (mutant p53, resistant to treatment) MJ: ↑~90% ATP depletion in both cell types 2DG, high Glc, but not pyruvate: ↓ ATP CJ, MJ 0.5–2.5 mM Nonsmall cell lung cancer lines A549 and H520 ↓ proliferation, cell cycle arrest at G2 /M phase ↑p38 and ERK1/2 phosphorylation ↑Bax↑p21 ↑caspase-3 [37 ] MJ 0.5–2.0 mM Hormone-refractory prostate adenocarcinomas PC-3, DU-145 ↓ proliferation ↑apoptosis ↓ 5-LOX[47 ] MJ 1–2.6 mM/EtOH—(IC50 ) Murine melanoma cells B16F10 and B16 COL/R (overexpressing Pgp, MDR) ↓ cell motility ↓ cell growth ↓ MDR[39 ] TBrJA (synthetic) 40 μ M/EtOH (MJ doses lower than in vitro ) Melanoma B16-F10 Breast MCF-7 Pancreas Mia PCA-2 D122, PBL ↑citoxicity (TBrJA ≫ MJ) [39 ] MJ 0.5–3.0 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 ] MJ 1.0-2.0 mM Human neuroblastoma BE(2)-C Arrest at S-phase ↓ cell growth↓ XIAP mRNA ↓ survivin mRNA ↑apoptosis [43 ] MJ
0.5–3.0 mM/DMSO Human breast cancer MCF-7 Human melanocytic MDA-MB-435 cells [74 ] Arrest at G0 /G1 and S-phase ↓ membrane fluidity ↑apoptosis: extrinsic (TNFR1, ↑caspase-8); intrinsic [↓ Δ
↑caspase-3 (only MDA-MB-435)] [25 ] CJ, MJ 2.0 mM/DMSO Hormone-independent prostate PC-3, DU-145 cells Cell cycle arrest ↓ cell growth ↑apoptosis (↑TNFR1, ↑caspase-3) [48 ]
JA, CJ, and MJ
1.0-2.0 mM/DMSO Human neuroblastoma SH-SY5Y Arrest at G2 /M phase ↓ cell growth ↑apoptosis (↓ XIAP ↓ survivin) activities: MJ > JA > CJ
[44 ] Human embryonic kidney HEK 293 cells Not affected by MJ MJ 1.0-2.0 mM/DMSO Human neuroblastoma SK-N-SH, BE(2)-C Arrest at G0 /G1 phase ↓ cell viability ↓ mRNA of PCNA ↑apoptosis (↓ XIAP ↓ survivin) [45 ] MJ 0.5–3.0 mM/EtOH Sarcomas: MCA-105, ↑pAkt (correlates with lower sensitivity to cytotoxicity by MJ) [49 ] SaOS-2 (resistent to MJ) MJ + 2DG: ↑cytotoxicity MJ 1.0–5.0 mM/EtOH Cervical 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[26 ] JA, MJ 0.25–4.0 mM/EtOH Acute myelogenous leukemia cells HL-60 and KG1 ↑ROS ↑MJ-induced mitochondrial membrane depolarization ↑MJ-induced Mit. SOD ↓ AKRC1 [132 ] MJ, MDDHJ 0.15 mM/DMSO Leukemia HL-60 cells ↑Ca2+ -binding protein S100P ↑differentiation ↑regulator of G-protein signaling-16 (RGS16) [42 ] J7 (synthetic) IC50 15 μ M Human cervical carcinoma HeLa cells Cell cycle arrest at G2 /M phase, ↓ Bcl-2 (caspase 9, 3) DNA damage [27 ] J7 (synthetic) 50 µ M/DMSO Human 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 [105 ] MJ 0.25–1.0 mM no vehicle reported Human colorectal cancer cells CRC ↑TRAIL ↑cyt c release ↑caspase cleavage ↓ survivin ↓ TCF transcriptional activity [32 ] MJ 0.0–2.0 mM/EtOH Cervical cancer cells SiHa, CaSki, HeLa, and C33A ↑mitochondrial
(HeLa, CaSki)↓ survivin ↓ E6, E7 (HPV) ↑different cell death pathways (independently of HPV) [28 ] J7 (synthetic) 0–50 μ M/ DMSO Human hepatoma HepG2 ↑ROS ↑TRAIL-mediated apoptosis (↓ Bid ↓ XIAP ↓ cIAP ↓ Bcl-xL ↑caspases) [35 ] MJ 3.0 mM (IC50 ) no vehicle reported Human adenocarcinoma colon HT-39 Arrest at S-G2 /M ↑cytotoxicity ↑apoptosis [31 ] JA, MJ 1.0–3.0 mM/DMSO Canine macrophagic malignant DM62 cells ↓ cell growth (MJ > JA) ↑cytotoxicity [256 ] MJ 0.5–0.2 mM/DMSO Human gastric SGC-7901, MKN-45 cell lines ↓ migration ↓ invasion ↓ angiogenesis ↓ MMP-14[33 ]