#2-Acetyl naphthalene

[rnomics]

Cells, Vol. 8, Pages 1466: Acetylshikonin Sensitizes Hepatocellular Carcinoma Cells to Apoptosis through ROS-Mediated Caspase Activation

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown strong and explicit #cancer cell-selectivity, which results in little toxicity toward normal tissues, and has been recognized as a potential, relatively safe anti#cancer agent. However, several #cancers are resistant to the apoptosis induced by TRAIL. A recent study found that shikonin b (alkannin, 5,8-dihydroxy-2-[(1S)-1-hydroxy-4-methylpent-3-en-1-yl]naphthalene-1,4-dione) might induce apoptosis in TRAIL-resistant cholangiocarcinoma cells through reactive oxygen species (ROS)-mediated caspases activation. However, the strong cytotoxic activity has limited its potential as an anti#cancer drug. Thus, the current study intends to discover novel shikonin derivatives which can sensitize the liver #cancer cell to TRAIL-induced apoptosis while exhibiting little toxicity toward the normal hepatic cell. The trypan blue exclusion assay, western blot assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay as well as the ‘comet’ assay, were used to study the underlying mechanisms of cell death and to search for any mechanisms of an enhancement of TRAIL-mediated apoptosis in the presence of ASH. Herein, we demonstrated that non-cytotoxic doses of acetylshikonin (ASH), one of the shikonin derivatives, in combination with TRAIL, could promote apoptosis in HepG2 cells. Further studies showed that application of ASH in a non-cytotoxic dose (2.5 μM) could increase intracellular ROS production and induce DNA damage, which might trigger a cell intrinsic apoptosis pathway in the TRAIL-resistant HepG2 cell. Combination treatment with a non-cytotoxic dose of ASH and TRAIL activated caspase and increased the cleavage of PARP-1 in the HepG2 cell. However, when intracellular ROS production was suppressed by N-acetyl-l-cysteine (NAC), the synergistic effects of ASH and TRAIL on hepatocellular carcinoma (HCC) cell apoptosis was abolished. Furthermore, NAC could alleviate p53 and the p53 upregulated modulator of apoptosis (PUMA) expression induced by TRAIL and ASH. Small (or short) interfering #RNA (#siRNA) targeting PUMA or p53 significantly reversed ASH-mediated sensitization to TRAIL-induced apoptosis. In addition, Bax gene deficiency also abolished ASH-induced TRAIL sensitization. An orthotopical HCC implantation mice model further confirmed that co-treated ASH overcomes TRAIL resistance in HCC cells without exhibiting potent toxicity in vivo. In conclusion, the above data suggested that ROS could induce DNA damage and activating p53/PUMA/Bax signaling, and thus, this resulted in the permeabilization of mitochondrial outer membrane and activating caspases as well as sensitizing the HCC cell to apoptosis induced by TRAIL and ASH treatment. http://bit.ly/2Oud8MW

[entirelysafe]

Flammability Level of various Substances

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Flammability Level of various Substances

Substance LFL/LEL in %

by volume of air

UFL/UEL in %

by volume of air

Flash point Auto-ignition

temperature

Acetaldehyde 4.0 57.0 -39 °C 175 °C Acetic acid (glacial) 4 19.9 39 °C to 43 °C 463 °C Acetic anhydride 54 °C Acetone 2.6–3 12.8–13 -17 °C 465 °C, 485 °C Acetonitrile 2 °C 524 °C Acetyl chloride 7.3 19 5 °C 390 °C Acetylene 2.5 100 Flammable gas 305 °C Acrolein 2.8 31 -26 °C Acrylonitrile 3.0 17.0 0 °C Allyl chloride 2.9 11.1 -32 °C Ammonia 15 28 11 °C 651 °C Arsine 4.5–5.1 78 Flammable gas Benzene 1.2 7.8 -11 °C 560 °C 1,3-Butadiene 2.0 12 -85 °C Butane, n-butane 1.6 8.4 -60 °C 420���500 °C n-Butyl acetate, butyl acetate 1–1.7 8–15 24 °C 370 °C Butyl alcohol, butanol 1 11 29 °C n-Butanol 1.4 11.2 35 °C 340 °C n-Butyl chloride, 1-chlorobutane 1.8 10.1 -6 °C n-Butyl mercaptan 1.4 10.2 2 °C 225 °C Butyl methyl ketone, 2-hexanone 1 8 25 °C 423 °C Butylene, 1-butylene, 1-butene 1.98 9.65 -80 °C Carbon disulfide 1.0 50.0 -30 °C 90 °C Carbon monoxide 12 75 -191 °C Flammable gas 609 °C Chlorine monoxide Flammable gas 1-Chloro-1,1-difluoroethane 6.2 17.9 -65 °C Flammable gas Cyanogen 6.0–6.6 32–42.6 Flammable gas Cyclobutane 1.8 11.1 -63.9 °C 426.7 °C Cyclohexane 1.3 7.8–8 -18 °C to -20 °C 245 °C Cyclohexanol 1 9 68 °C 300 °C Cyclohexanone 1–1.1 9–9.4 43.9–44 °C 420 °C Cyclopentadiene 0 °C 640 °C Cyclopentane 1.5–2 9.4 -37 to -38.9 °C 361 °C Cyclopropane 2.4 10.4 -94.4 °C 498 °C Decane 0.8 5.4 46.1 °C 210 °C Diborane 0.8 88 -90 °C Flammable gas 38 °C o-Dichlorobenzene, 1,2-dichlorobenzene 2 9 65 °C 648 °C 1,1-Dichloroethane 6 11 14 °C 1,2-Dichloroethane 6 16 13 °C 413 °C 1,1-Dichloroethene 6.5 15.5 -10 °C Flammable gas Dichlorofluoromethane 54.7 Non flammable,-36.1 °C 552 °C Dichloromethane, methylene chloride 16 66 Non flammable Dichlorosilane 4–4.7 96 -28 °C Diesel fuel 0.6 7.5 >62 °C (143 °F) 210 °C Diethanolamine 2 13 169 °C Diethylamine 1.8 10.1 -23 to -26 °C 312 °C Diethyl disulfide 1.2 38.9 °C Diethyl ether 1.9–2 36–48 -45 °C 160–170 °C Diethyl sulfide -10 °C 1,1-Difluoroethane 3.7 18 -81.1 °C 1,1-Difluoroethylene 5.5 21.3 -126.1 °C Diisobutyl ketone 1 6 49 °C Diisopropyl ether 1 21 -28 °C Dimethylamine 2.8 14.4 Flammable gas 1,1-Dimethylhydrazine Dimethyl sulfide -49 °C Dimethyl sulfoxide 2.6–3 42 88–95 °C 215 °C 1,4-Dioxane 2 22 12 °C Epichlorohydrin 4 21 31 °C Ethane 3 12–12.4 Flammable gas -135 °C 515 °C Ethanol, ethyl alcohol 3–3.3 19 12.8 °C (55 °F) 365 °C 2-Ethoxyethanol 3 18 43 °C 2-Ethoxyethyl acetate 2 8 56 °C Ethyl acetate 2 12 -4 °C 460 °C Ethylamine 3.5 14 -17 °C Ethylbenzene 1.0 7.1 15–20 °C Ethylene 2.7 36 490 °C Ethylene glycol 3 22 111 °C Ethylene oxide 3 100 -20 °C Ethyl chloride 3.8 15.4 -50 °C Ethyl mercaptan Fuel oil No.1 0.7 5 Furan 2 14 -36 °C Gasoline (100 octane) 1.4 7.6 < -40 °C (-40 °F) 246–280 °C Glycerol 3 19 199 °C Heptane, n-heptane 1.05 6.7 -4 °C 204–215 °C Hexane, n-hexane 1.1 7.5 -22 °C 225 °C, 233 °C Hydrogen 4/18.3 75/59 Flammable gas 500–571 °C Hydrogen sulfide 4.3 46 Flammable gas Isobutane 1.8 9.6 Flammable gas 462 °C Isobutyl alcohol 2 11 28 °C Isophorone 1 4 84 °C Isopropyl alcohol, isopropanol 2 12 12 °C 398–399 °C; 425 °C Isopropyl chloride Kerosene Jet A-1 0.6–0.7 4.9–5 >38 °C (100 °F) as jet fuel 210 °C Lithium hydride 2-Mercaptoethanol Methane (natural gas) 5.0 15 Flammable gas 580 °C Methyl acetate 3 16 -10 °C Methyl alcohol, methanol 6–6.7 36 11 °C 385 °C; 455 °C Methylamine 8 °C Methyl chloride 10.7 17.4 -46 °C Methyl ether -41 °C Methyl ethyl ether Methyl ethyl ketone 1.8 10 -6 °C 505–515 °C Methyl formate Methyl mercaptan 3.9 21.8 -53 °C Mineral spirits 0.7 6.5 38–43 °C 258 °C Morpholine 1.8 10.8 31–37.7 °C 310 °C Naphthalene 0.9 5.9 79–87 °C 540 °C Neohexane 1.19 7.58 -29 °C 425 °C Nickel tetracarbonyl 2 34 4 °C 60 °C Nitrobenzene 2 9 88 °C Nitromethane 7.3 22.2 35 °C 379 °C Octane 1 7 13 °C iso-Octane 0.79 5.94 Pentane 1.5 7.8 -40 to -49 °C 260 °C n-Pentane 1.4 7.8 iso-Pentane 1.32 9.16 420 °C Phosphine Propane 2.1 9.5–10.1 Flammable gas 480 °C Propyl acetate 2 8 13 °C Propylene 2.0 11.1 -108 °C 458 °C Propylene oxide 2.9 36 Pyridine 2 12 20 °C Silane 1.5 98 <21 °C Styrene 1.1 6.1 31–32.2 °C 490 °C Tetrafluoroethylene Tetrahydrofuran 2 12 -14 °C 321 °C Toluene 1.2–1.27 6.75–7.1 4.4 °C 480 °C; 535 °C Triethylborane -20 °C -20 °C Trimethylamine Flammable gas Trinitrobenzene Turpentine 0.8 35 °C Vegetable oil 327 °C (620 °F) Vinyl acetate 2.6 13.4 -8 °C Vinyl chloride 3.6 33 Xylenes 0.9–1.0 6.7–7.0 27–32 °C m-Xylene 1.1 7 25 °C 525 °C o-Xylene 17 °C p-Xylene 1.0 6.0 27.2 °C 530 °C