Compound Antitumor activity and/or mechanism Animal/cell line tested IC50 , Reference
Active (cell cycle arrest; induction of apoptosis)
[13 ] Human colon cancer cell lines HCT-116 (p53−/−) 10–30%
Active (cell cycle arrest; induction of apoptosis)
[13 ] Human colon cancer cell lines HCT-116 (p53−/−) 10–30% HeLa (epithelioid carcinomic cell line) ND Active (ND) MOLT-4 (human lymphoblastic leukemia T-cell line) ND [14 ] K-562 (human chronic myelogenous leukemia cell line) ND CTVR-1 (early B-cell line from the bone marrow cells of a patient with acute myeloid leukemia) ND µ g/mL 15 ] Active (inhibition of the NF-κ B pathway) Small cell lung carcinoma 0.26 mM [16 ] Active (ND) Mouse P388 leukemia cell 34–54 µ g/mL* [17 ] in vitro ) in vivo ) 18 ] Active (inhibition gene expression of topoisomerases I, II alpha, and II beta and promoting the gene expression of NF-κ B) SNU-5 (human gastric carcinoma cell line) 1.62 mg/mL [19 ] α ,25-dihydroxyvitamin D3) 20 ] Active (TRPM8 channel activation; cell cycle arrest) DU145 (human prostate carcinoma cell line) 53.41–90.66% [21 ] Active (mitochondrial membrane depolarization via the TRPM8 channel) T24 (Human bladder cancer cell line) ND [22 ] Active (agonist of TRPM8) Oral squamous carcinoma cell lines (HSC3 and HSC4) ND [23 ]
Active (ND) b
[24 ] Ehrlich's ascites carcinoma 75%b
Active (ND) b
[25 ] Ehrlich's ascites carcinoma 87%b
Active (ND) b
[24 ] Ehrlich's ascites carcinoma 91%b
Active (ND) µ M
[26 ] Caco-2 (colon malignant cell line) 2250 µ M
Active (potentiates selenocystine-induced apoptosis and activation of ROS-mediated DNA damage) HepG2 (hepatocellular carcinomic human cell line) ND
[27 ] Active (ND) HL60 (acute promyelocytic cancer cell line) ND [28 ] MDA-MB-231 (Human metastatic breast cancer cell line) ND Active (ND) HL-60 (acute promyelocytic cancer cell line) 6.3 µ g/mL
[29 ] HCT-8 (ileocecal colorectal adenocarcinoma) 18.4 µ g/mL Active (ND) Sarcoma 180 (in vivo ) 10 or 20 mg/kg [29 ] Active (ND) Mouse leukemia P388 cell line ND [30 ] P815 (mastocytoma cell line) <0.004% v/v [31 ] P815 (mastocytoma cell line) 1.2% v/v · 10−2 [39 ] K-562 (human chronic myelogenous leukemia) 1.2% v/v · 10−2 [39 ] Active (cell cycle arrest; induction of apoptosis) CEM (acute T lymphoblastic leukemia) 1.2% v/v · 10−2 [39 ] MCF-7 (human breast adenocarcinoma) 2.5% v/v · 10−2 [39 ] MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) 0.85% v/v · 10−2 [39 ] P815 (mastocytoma cell line) 0.067 µ M [46 ] K-562 (human chronic myelogenous leukemia) 0.067 µ M [46 ] CEM (acute T lymphoblastic leukemia) 0.042 µ M [46 ] Active (cell cycle arrest; induction of apoptosis) MCF-7 (human breast adenocarcinoma) 0.125 µ M [46 ] MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) 0.067 µ M [46 ] Active (induction of apoptosis) Hep2 (larynx epidermoid carcinoma) 0.22–0.32 mM* [35 ] Active (induction of apoptosis) HepG2 (hepatocellular carcinomic human cell line) 0.4 mmol/L [36 ] Active (induction of apoptosis) MDA-MB 231 (human metastatic breast cancer cell line) 100 μ M [37 ] HepG2 (hepatocellular carcinomic human cell line) ND [32 ] Active (antioxidant activity) Caco-2 (colon malignant cell line) ND [32 ] K562 (erythromyeloblastoid leukemia cell line) 150–200 μ M [33 ] Active (ND) HepG2 (hepatocellular carcinomic human cell line) 350 μ M
[34 ] Caco-2 (colon malignant cell line) 600 μ M 1 DMBA in rats 43 ] Myoblast cells 60 μ g/mL [40 ] Active (prevention of hepatocellular carcinogenesis) DEN-induced hepatocellular carcinogenesis 15 mg/kg [38 ] Active (ND) HepG2 (hepatocellular carcinomic human cell line) 53.09 μ g/mL [42 ] Active (ND) Mouse leukemia P388 cell line 1.1 µ g/mL [44 ] 30 ] HepG2 (hepatocellular carcinomic human) >25 µ g/mL Active (cell cycle arrest; induction of apoptosis) K562 (erythromyeloblastoid leukemia cell line) ND [9 ] B16-F10 (melanoma) 9.28 µ g/mL Active (ND) Hep-2 (larynx epidermoid carcinoma) 0.71–0.78 mM* [35 ] Active (ND) HepG2 (hepatocellular carcinomic human cell line) 400 μ M
[34 ] Caco-2 (colon malignant cell line) 700 μ M Active (ND) Mouse leukemia P388 cell line ND [30 ] Active (ND) Mouse leukemia P388 cell line 0.80 µ g/mL [44 ] P815 (mastocytoma cell line) 0.015% v/v [31 ] P815 (mastocytoma cell line) 3.1% v/v · 10−2 [39 ] K-562 (human chronic myelogenous leukemia) >22% v/v · 10−2 [39 ] Active (cell cycle arrest and apoptosis) CEM (acute T lymphoblastic leukemia) 6.9% v/v · 10−2 [39 ] MCF-7 (human breast adenocarcinoma) >22% v/v · 10−2 [39 ] MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) >22% v/v · 10−2 [39 ] P815 (mastocytoma cell line) 0.15 µ M [46 ] K-562 (human chronic myelogenous leukemia) 0.44 µ M [46 ] CEM (acute T lymphoblastic leukemia) 0.31 µ M [46 ] Active (cell cycle arrest and apoptosis) MCF-7 (human breast adenocarcinoma) 0.48 µ M [46 ] MCF-7 gem (human breast adenocarcinoma resistant to gemcitabine) ND [46 ] HepG2 (hepatocellular carcinomic human cell line) ND [32 ] Active (antioxidant activity) Caco-2 (colon malignant cell line) ND [32 ] K562 (erythromyeloblastoid leukemia cell line) 400–500 µ M [33 ] Active (cell cycle arrest; induction of apoptosis) HL-60 (acute promyelocytic cancer cell line) ND [12 ] Active (ND) HepG2 (hepatocellular carcinomic human cell line) 60.01 µ g/mL [42 ] c Active (ND) Fibrosarcoma (FsaR) cell lines (in vitro ) 92%c [47 ] Fibrosarcoma (FsaR) cell lines (in vivo ) 20 mg/kg A549 (lung carcinoma cell line) 72.0–146 µ M* Active (induction of apoptosis) HEp-2 (larynx epidermoid carcinoma cell line) 22.9–34.6 µ M*
[49 ] HT-29 (colon adenocarcinoma cell line) 51.0–53.3 µ M* MIA PaCa-2 (pancreas carcinoma cell line) 60.0–67.9 µ M* SF-539 (central nervous system cancer cell line) ND PC-3 (prostate cancer cell line) ND Active (ND) M-14 (melanoma) ND [48 ] OVCAR-5 (ovarian cancer cell line) ND MCF-7 (breast adenocarcinoma cell line) ND Active (ND) A-549 (lung carcinoma cell line) 13.0 µ M
[50 ] DLD-1 (colorectal adenocarcinoma cell line) 5.9 µ M SCC VII (squamous cell carcinoma) 86%c Active (ND) Fibrosarcoma (FsaR) cell lines (in vitro ) 92%c [47 ] Fibrosarcoma (FsaR) cell lines (in vivo ) 20 mg/kg Active (proteasome inhibition and induction of apoptosis) U87 MG (malignant glioma cells) 61.46–77.73 µ M* µ M* [51 ] Active (induction of apoptosis) NCI-H460 (nonsmall cell lung cancer cell line) ND [52 ] Active (downregulation of NF- Mouse xenograft model using NCI-H460 (human large cell lung cancer) 20 mg/kg [52 ] Active (suppression of the NF- KBM-5 (human myeloid cell line) ND [56 ] Active (suppression of STAT3 activation and induction of apoptosis) Multiple myeloma ND [58 ] Active (inactivation of the stress response pathway sensor CHEK1 and induction of apoptosis) Human colon cancer cell lines ND [57 ] Active (ND) Ehrlich ascites carcinoma bearing mice 50 mg/L [53 ] 54 ] Active (downregulation of NF- Orthotopic model of pancreatic cancer (in vitro ) in vivo ) ND [55 ] 86 ] Active (antioxidant activity) Fibrosarcoma induced by 20-methylcholanthrene (MC) in male Swiss albino mice (in vitro ) in vivo ) ND [59 ] 60 ] Active (antioxidant activity) Osteoblasts cells (MG 63) in tissue culture 32–64% [61 ] µ M µ M 62 ] Active (inhibition of NF-κ B and antiangiogenesis effect) Osteosarcoma (in vitro ) in vivo ) ND [63 ] Active (induction of apoptosis via p53-dependent pathway) HeLa (epithelioid carcinomic cell line) 2.80–5.93 mg/mL* [64 ] Active (involvement of reactive oxygen species and activation of ERK and JNK signaling) Caco-2 (human colon cancer cell) 12.5–15.0 µ M*
[65 ] HCT-116 (human colon cancer cell) 14–30 µ M* LoVo (human colon cancer cell) 28–38 µ M* DLD-1 (human colon cancer cell) 23–42 µ M* HT-29 (human colon cancer cell) 110 µ M Active (binding to bovine serum albumin) DLD-1 (human colon cancer cell) ND
[88 ] HCT-116 (human colon cancer cell) ND Active (ND) A549 (human nonsmall cell lung cancer (NSCLC) cell line) ND [67 ] Active (antioxidant activity) ES-2 (ovarian cancer cell line) ND [66 ] Active (prooxidant cytotoxic mechanism) Prostate cancer cell lines ND [68 ] Active (ND) 66 cl-4-GFP (resistant mouse mammary gland cell line) in vivo 10 mg/kg [69 ] Active (disruption in cell-cycle checkpoints) LNCaP (prostate cancer cell line) ND [70 ]71 ] Active (induction of apoptosis) p53-null myeloblastic leukemia HL 60 cells 23 µ M [72 ] Active (increase of ROS generation and decreased GSH levels) Androgen receptor (AR) independent (C4-2B) 100
[73 ] AR naive (PC-3) prostate cancer cells 86 Active (cell cycle arrest; induction of apoptosis) COS31 (canine osteosarcoma) ND [74 ] Active (cell cycle arrest; induction of apoptosis) HepG2 (hepatocellular carcinomic human cell line) 350 µ M [75 ] Active (cell cycle arrest, increase in the expression of the protein p53 and decrease in cyclin B1 protein) Primary mouse keratinocytes, SP-1 (papilloma) 30 µ Mµ M [76 ] Active (inhibition of telomerase) Human glioblastoma cells ND [77 ] Active (inhibition of PDE1A expression) Jurkat cell (acute lymphoblastic leukemia cell line) ND [79 ] Active (downregulated MUC4 expression and induction of apoptosis) The MUC4-expressing pancreatic cancer cells FG/COLO357 73 μ mol/Lμ mol/L
[80 ] Active (upregulation of PTEN expression and induction of apoptosis) Doxorubicin-resistant human breast cancer MCF-7/DOX cell 35–70%a [82 ] Active (ND) Parental and multidrug resistant (MDR) human tumor cell lines 78 µ M [81 ] Active (thymoquinone-loaded nanoparticles activity) MDA-MB-231 (human metastatic breast cancer cell line) ND [84 ] Active (comparison of thymoquinone versus thymoquinone-loaded nanoparticles activities) HCT-116 (colon cancer cell line) 15% versus 85%b [83 ] MCF-7 (breast cancer cell line) 30% versus 88%b PC-3 (prostate cancer cell line) 30% versus 85%b U-266 (multiple myeloma cell line) 55% versus 70%b HCT116 (colon cancer cell line) 24%c Activity of derivatives of thymoquinone HCT116p53−/− colon cancer 72%c [85 ] HepG2 (hepatocellular carcinomic human cell line) 75%c HL-60 (acute promyelocytic leukemia cells) 0.13–>100 µ M* Activity of analogs of thymoquinone 518A2 (melanoma cell line) 3.9–>100 µ M*
[87 ] multidrug-resistant KB-V1/Vbl cervix 7.0–79.9 µ M* MCF-7/Topo (breast carcinoma) 2.8–>100 µ M* Active (ND) Mouse Ehrlich ascites carcinoma tumor ND [89 ] Active (inhibition of Akt phosphorylation; induction of apoptosis; inhibition of HDAC2 proteins) LNM35 (human lung cancer cell) 50–78 µ M* HepG2 (human hepatoma cell) 34 µ M HT29 (human colorectal cancer cell) 50–78 µ M*
[96 ] MDA-MB-435 (human mammary adenocarcinoma cell) 50–78 µ M* MDA-MB-231 (human mammary adenocarcinoma cell) 50–78 µ M* MCF-7 (human mammary adenocarcinoma cell) 50–78 µ M* Active (ND) In vivo activity of quinone reductase and glutathione transferase in mice liver1, 2 or 4 mg/kg [90 ] Active (cell cycle arrest; induction of apoptosis via Akt modulation) MDA-MB-468 (human mammary adenocarcinoma) 12.30 µ M
[92 ] T-47D (human mammary ductal carcinoma) 18.06 µ M Active (induction of apoptosis) HL-60 (human promyelocytic leukemia cell) 27.8 µ M
[93 ] 518A2 (melanoma cell line) 28.3 µ M HT-29 (colon carcinoma cell) 46.8 µ M Active (induction of apoptosis) KB-V1 (cervix carcinoma cell) 25.8 µ M
[93 ] MCF-7 (human mammary adenocarcinoma cell) 20.1 µ M Multidrug-resistant variants 18.7–57.2 µ M* MCF-7 (breast cancer cell line) 32–48 µ M* Active (modulation of the PPAR-γ activation pathway) MDA-MB-231 (breast cancer cell line) 11–24 µ M* [193 ] BT-474 (breast cancer cell line) 18–38 µ M* Active (condition T cells in vitro for adoptive T cell therapy against cancer and infectious disease) OT-1 (transgenic CD8+) T cells ND [95 ] Active (induction of apoptosis) Mouse model of familial adenomatous polyposis 375 mg/kg [97 ] Active (comparison of thymoquinone and thymoquinone in liposomes effects) MCF-7 (breast cancer cell line) 40 µ M versus 200 µ Mµ M versus 75 µ M [99 ] A431 (human epidermoid carcinoma) 10 µ M Active (cell cycle arrest and induction of apoptosis) Hep-2 (larynx epidermoid carcinoma) 10 µ M [100 ] Sarcoma 180 in vivo 10 mg/kg
Active (antimicrotubule drug)
[101 ] Jurkat cells (acute lymphoblastic leukemia cell line) ND Active Mouse P388 leukemia cell ND [17 ] HeLa (human cervical carcinoma) >200 µ g/mL Active (ND) A-549 (human lung carcinoma) >200 µ g/mL [103 ] HT-29 (human colon adenocarcinoma) cell lines >200 µ g/mL Crown gall tumors 50%b Active (ND) MCF-7 (breast carcinoma)
<
[102 ] HT-29 (colon adenocarcinoma) < A-549 (lung carcinoma) < Active (cell cycle arrest and induction of apoptosis) HepG2 (hepatocellular carcinomic human cell line) 9.23 µ g/mL
[9 ] B16F10 (murine melanoma) 12.27 µ g/mL Active (cell cycle arrest and induction of apoptosis) B16F10 (murine melanoma) 12.27 µ g/mL [9 ] Active (induction of the hepatic detoxification enzymes glutathione S-transferase GST and uridine diphosphate-glucuronosyltransferase UDPGT) DMBA-induced rat mammary carcinogenesis ND [104 ] Active (antitumorigenic effects induction of apoptosis) Pancreatic, mammary, and prostatic tumors ND [105 ] Active (inhibition of the isoprenylation of small G proteins) DMBA- and 5 NMU-induced rat mammary carcinomas 10% in diet [114 ] Active (combined limonene and 4-hydroxyandrostrenedione) NMU-induced rat mammary carcinomas 5% limonene and 4-hydroxyandrostrenedione (12.5 mg/kg) [115 ] Active (ND) DMBA-induced rat mammary carcinogenesis ND [116 ] Active (induction of apoptosis and antiangiogenic effect) SW480 (human colorectal adenocarcinoma) ND [117 ] Active (induction of apoptosis and antiangiogenic effect) HT-29 (colon adenocarcinoma) ND [117 ] Active (immunomodulatory effect) BW5147 (murine T cell lymphoma) 35 µ g/mL [118 ] Active (ND) B16F-10 (melanoma cells in mice) 100 µ M/kg [119 ] Active (induction of the hepatic detoxification enzymes glutathione S-transferase GST and uridine diphosphate-glucuronosyltransferase UDPGT) DMBA-induced rat mammary carcinogenesis ND [104 ] Activity of derivatives limonene (inhibition of protein prenylation) In vitro assays with mammalian and yeast farnesyltransferase (PFT) and geranylgeranyltransferase (PGGT) proteinsND [107 ] Active (inhibition of NNK metabolic activation) NNK-induced lung tumorigenesis in mice 183 µ mol [120 ] Active (ND) AflatoxinB1-induced hepatocarcinogenesis 5% in diet [121 ] Active (induction of apoptosis) K562 (erythromyeloblastoid leukemia cell line) ND [110 ] Active (ND) Colonic carcinogenesis in rats 5% [111 ] Active (high affinity with HMG-CoA reductase) in silico approachesND [112 ] Active (increase of GST activity) Several tissues of female A/J mice 20 mg/0.3 mL of the oil [122 ] MCF-7 (human breast adenocarcinoma) 14 µ g/mL Active (ND) K562 (erythromyeloblastoid leukemia cell line) 16 µ g/mL [106 ] PC12 (rat adrenal pheochromocytoma cell line) >100 µ g/mL A-549 (lung carcinoma) <10 Active (ND) MCF-7 (breast carcinoma) <10 [102 ] HT-29 (colon adenocarcinoma) <10 A-549 (lung carcinoma) ND Active (effect on gap junction intercellular communication) W1-38 (human fibroblast lung normal cells) ND [113 ] CACO2 (human colorectal adenocarcinoma) ND 113 ]
Active (ND) A-549 (lung carcinoma) 0.098
[108 ] HepG2 (hepatocellular carcinomic human cell line) 0.150 Active (ND) Molecular docking ND [109 ] Active (involvement of c-myc oncoprotein) NDEA induced hepatocarcinogenesis 5% in diet [123 ] c Active (cell cycle arrest; induction of apoptosis) SCC-25 (human head and neck squamous cell carcinoma cell line) 19%c [126 ] BroTo (human head and neck squamous cell carcinoma cell line) 9%c Active (cell cycle arrest; induction of apoptosis) A549 (human lung adenocarcinoma) 3.6 mM [125 ] Active (induction of apoptosis) 9,10-Dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis 6 or 12 mg/kg [146 ] Active (cell cycle arrest; induction of apoptosis) Advanced rat mammary carcinomas 0.1 g/kg [147 ] Active (cell cycle arrest; induction of apoptosis) Bcr/Abl-transformed leukemia cells ND [148 ] Active (cell cycle arrest and induction of apoptosis) Bcr/Abl-transformed myeloid cell lines 300–400 µ m [139 ] Active (ND) Hamster pancreatic tumors 1.2–2.4 g/kg [127 ]
Active (ND) MIA PaCa2 (human pancreatic tumor cells) 60–90%2
[128 ] PC-1 (hamster pancreatic adenocarcinoma) 40 g/kg Active (induction of Bak-induced apoptosis) B12/13 (pancreatic adenocarcinoma cell line) 150 µ M [130 ] Active (inhibition of the prenylation of growth-regulatory proteins) Pancreatic adenocarcinoma cells ND [129 ] AsPC-1 (pancreatic adenocarcinoma cell line) 300 µ mol/L Active (induction of apoptosis) MIA PaCa-2 (pancreatic adenocarcinoma cell line) 350 µ mol/L [131 , 149 ] PANC-1 (pancreatic adenocarcinoma cell line) 350 µ mol/L BxPC-3 (pancreatic adenocarcinoma cell line) 550 µ mol/L Active (induction of apoptosis) K562 (erythromyeloblastoid leukemia cell line) 81.0 µ mol/L [133 ] Active (antiangiogenic activity) BLMVECs (bovine lung microvascular endothelial cells) ND [135 , 136 ] Active (c-Myc-dependent apoptosis) Bcr/Abl-transformed leukemia cells ND [134 ] Active (cell cycle arrest; induction of apoptosis) A549 (human lung adenocarcinoma epithelial cell line) 1.4 mM [125 ] Active (inhibition of Na+ /K+ -ATPase activity) Guinea pig brain and kidney were used in the preparation of homogenates and Na/K-ATPase-enriched fractions 1.0 mM for the brain enzyme and 1.5 mM for the kidney enzyme [137 ] Active (inhibition of protein isoprenylation and cell proliferation) HT-29 (colon adenocarcinoma cell) ND [138 ] Active (modulation of the expression of AP-1 target genes) Breast cancer cells ND [140 ] Active (antitumor effect potentiated by hyperthermia) SCK mammary carcinoma cells of A/J mice
20–58%a [141 ] Active (inhibition of ubiquinone synthesis and block of the conversion of lathosterol to cholesterol) NIH3T3 (mouse fibroblast cell line) ND [142 ] Active (activity of metabolites of perillyl alcohol) Inhibition of protein prenyltransferases in vitro 1 mM [107 ] Active (inhibition of the in vivo prenylation of specific proteins) NIH3T3 (mouse fibroblast cell line) 0.5 or 1.0 mM [143 ] Active (ND) AflatoxinB1-induced hepatocarcinogenesis 2% in diet [121 ] Active (antimetastatic activity) C6 (glial cell line) ND [144 ] Active (phases I/II study) Human malignant gliomas 0.3% v/v [145 ] Active (pretreated before exposure to radiation) HTB-43 (head and neck squamous cell carcinoma cell line) 71%b [126 ] b 126 ] BroTo (head and neck squamous cell carcinoma cell line) 53%b Active (radio-/Chemosensitizer) Glioma cells ND [152 ] Active (cell cycle arrest; induction of apoptosis) PC12 (rat adrenal pheochromocytoma cell line) ND [150 ] Active (pharmacokinetics studies) Pharmacokinetics studies in dogs ND [151 ] Active (phase I) Human advanced malignancies 800–2400 mg/m2 /dose [153 ] Active (telomerase activity) Prostate cancer cells ND [132 ] Active (ND) HepG2 (hepatocellular carcinomic human cell line); ND [14 ] 2 2
[159 ] Active (induction of apoptosis) KB (human papilloma cell line) ND [160 ] SK-OV-3 (human ovarian adenocarcinoma) 1.10 Active (ND) HO-8910 (human epithelial ovarian cancer) 2.90 [158 ] Bel-7402 (human hepatocellular carcinoma) 3.47 Active (binds to the Caspase 3) Molecular docking studies ND [109 ] Active (ND) K-562 (human chronic myelogenous leukemia cell line) ND [106 ] PC-12 (rat adrenal gland pheochromocytoma) ND HepG2 (hepatocellular carcinomic human cell line) ND HeLa (epithelioid carcinomic cell line) ND Active (ND) MOLT-4 (human lymphoblastic leukemia T-cell line) ND [14 ] K-562 (human chronic myelogenous leukemia cell line) ND CTVR-1 (early B cell line from the bone marrow cells of a patient with acute myeloid leukemia) ND Active (induction of apoptosis) Human melanoma M14 WT cells and their resistant variants ND [161 ] Active (ND) Drug-sensitive and drug-resistant melanoma cells ND [162 ] Active (cell cycle arrest and induction of necrosis) AE17 (mesothelioma murine cancer cells) 0.01–0.02 [163 ] Active (ND) A-549 (lung carcinoma); DLD-1 >100 µ Mµ M [50 ] 164 ] Active (ND) MCF-7 (breast carcinoma) 92.3%c [165 ] Active (induction of apoptosis-activating p53) Endometrial cancer cell lines Ishikawa and ECC-1 (endometrial carcinoma cell line) 2.3 µ g/mL [166 ] Active (induction of apoptosis) NB4 (acute promyelocytic leukemia cell line) 3.995 µ g/mL [167 ] 35 ] Active (ND) HeLa (human cervical carcinoma) 74.5 µ g/mL [168 ] Active (induction of oxidative stress) Cultured primary rat neuron and N2a neuroblastoma (NB) cells ND [169 ] Active (ND) MCF-7 (breast carcinoma) 0.63 μ M
[46 ] K-562 (human chronic myelogenous leukemia cell line) 0.17 μ M P-815 (mouse lymphoblast like mastocytoma cell line) 0.16 μ M CEM (human acute lymphoblastic leukemia) 0.11 μ M Active (oxidative stress and reporter gene activities of antioxidant response element (ARE), activator protein 1 (AP-1), and nuclear factor NF- A549 (lung carcinoma) 250 ppm [174 ] Active (immunomodulatory effect) BW 5147 (murine T cell lymphoma) 1100 μ g/mLμ g/mL [118 ] HepG2 (hepatocellular carcinomic human cell) 1393.3 µ g/mL K562 (human chronic myelogenous leukemia cell line) 679.1 µ g/mL Active (ND) H-460 (lung large cell carcinoma) 501.8 µ g/mL [170 ] N-87 (gastric carcinoma) 840.6 µ g/mL SW-620 (colon adenocarcinoma) 786.2 µ g/mL Active (ND) Dual reverse virtual screening protocol ND [109 ] Active (ND) SK-OV-3 (human ovarian adenocarcinoma) 0.052 [158 ] Active (ND) Bel-7402 (human hepatocellular carcinoma) 0.32 [158 ] Active (ND) MCF-7 (mammary adenocarcinoma) 64.3 µ g/mL5 µ g/mL5 µ g/mL5 µ g/mL5 [171 ] Active (induction of apoptosis) U937 (histiocytic lymphoma cells) ND [172 ] HeLa (human cervical carcinoma) 172.7 μ g/mL Active (ND) A-549 (human lung carcinoma) 183.2 μ g/mL [103 ] HT-29 (human colon adenocarcinoma) >200 μ g/mL MCF-7 (human breast carcinoma cell line) 20.6 µ g/mL Active (ND) MDA-MB-468 (human breast carcinoma cell line) 39.2 µ g/mL [173 ] UACC-257 (human breast carcinoma cell line) 16.3 µ g/mL Active (ND) A-549 (lung carcinoma) 85.0 μ Mμ M [50 ] MCF-7 (breast carcinoma) Active (ND) A375 (human melanoma) ND [170 ] HepG2 (hepatocellular carcinomic human cell line) Active (immunomodulatory effect) BW5147 (murine T cell lymphoma) 114.81 μ g/mL [118 ] MCF-7 (breast carcinoma) 176.5–242.6 mM* Active (ND) A375 (human melanoma) 198.5–264.7 μ M* [91 ] HepG2 (hepatocellular carcinomic human cell) 147.1–198.5 μ M* Active (ND) MCF-7 (human breast carcinoma cells) ND [171 ] Active (ND) Dual reverse virtual screening protocol ND [109 ] Active (cell cycle arrest) (Caco-2) human colon cancer cell line 70%a [179 ] Active (blockade of the morphological and functional differentiation of the cells) Human colonic cancer cells 30%c [175 ] Caco-2 (human epithelial colorectal adenocarcinoma cells) 250 µ M Active (thymidylate synthase and thymidine kinase expression) SW620 (human colon adenocarcinoma) 330 µ M [176 ] TC-118 (colorectal tumor) 150 mg/kg Active (ND) Human MIA PaCa2 pancreatic tumor cells and hamster (transplanted PC-1 pancreatic adenocarcinomas) a [128 ] Active (effects on mevalonate and lipid metabolism) HepG2 (hepatocellular carcinomic human cell line) a [177 ] Active (high affinity with HMG-CoA reductase) HepG2 (hepatocellular carcinomic human cell line) ND [178 ] Active (high affinity with HMG-CoA reductase) In silico approachesND [112 ] Active (activity of the detoxifying enzyme glutathione S-transferase) Mucosa of the small intestine and large intestine ND [122 ] 180 ] Active (induction of apoptosis; inhibition of RhoA activation) Hepatocarcinogenesis in rats 25 mg/100 g [181 ] Active (ND) MIA PaCa2 (human pancreatic tumor cells) 60–90%a [128 ] Active (nuclear factor erythroid 2-related factor-2 (Nrf2) activation) 4NQO-induced oral carcinogenesis in mouse 200 mg/kg [182 ] Active (ND) Dual reverse virtual screening protocol ND [109 ] µ M 187 ] Active (ND) C32 (amelanotic melanoma cell line) 23.2 µ g/mL [94 ] Active (ND) HeLa (human cervical carcinoma cells) 0.37 µ g/mLµ g/mLµ g/mLµ g/mL 184 ] Active (ND) U2 OS (bone carcinoma cells) 21.7 µ g/mL [184 ] Active (ND) U937 (histiocytic lymphoma cell line) 3.51 µ g/mLµ g/mL [185 ] Active (induction of apoptosis by activation of p53 and CDKIs) Kasumi-1 (acute myeloid leukemia) 49.53–127.14 µ M HL-60 (acute myeloid leukemia) 49.53–127.14 µ M THP-1 (acute myeloid leukemia) >144.04 µ M U937 (acute myeloid leukemia) >144.04 µ M KG-1 (acute myeloid leukemia) >144.04 µ M NB4 (acute myeloid leukemia) >144.04 µ M [188 ] K562 (blast crisis of chronic myeloid leukemia) >144.04 µ M Molt-4 (acute T-lymphoblastic leukemia) 49.53–127.14 µ M H-9 (acute T-lymphoblastic leukemia) ND Jurkat (acute T-lymphoblastic leukemia) >144.04 µ M Raji (human Burkitt’s lymphoma) 49.53–127.14 µ M L428 (Hodgkin’s lymphoma) >144.04 µ M µ M 189 ] multidrug resistant MCF7 AdrR 1.24–3.0 µ M Active (ND) C32 (amelanotic melanoma cell line) 23.2 μ g/mL
[186 ] Renal adenocarcinoma cells 23.8 μ g/mL Active (induction of apoptosis; promotion cell differentiation) HL-60 (acute promyelocytic leukemia cells) ND [190 ] Active (combination of doxorubicin-linalool increased doxorubicin influx in tumor cells) Mouse P388leukemia cells (in vitro ) ND
[191 ] Mouse P388leukemia cells (in vivo ) 1.0 mg/kg/day Active (ND) A-549 (lung carcinoma) 43.0 µ g/mLµ g/mL [50 ] Active (ND) MCF-7 (human breast cancer cells) 1.3 mg/L [192 ]
