Mutagenicity of cigarette butt waste in the bacterial reverse mutation assay: The protective effects of β‐caryophyllene and β‐caryophyllene oxide

Abstract

Cigarette filters pose a serious litter and toxic waste disposal problem, because of their not biodegradability and to the leaching of toxins in the environment. Therefore, cigarette butts need to be manipulated as special waste, with potential risks to human health and environment. In the present study, the genotoxic potential of a methanol extract from commonly discharged cigarette butts (CBE) was evaluated in the bacterial reverse mutation assay on Salmonella typhimurium TA98 and TA100 and Escherichia coli WP2uvrA strains, both in the absence and presence of the S9 exogenous metabolic activator. Furthermore, the ability of the natural sesquiterpenes β-caryophyllene (CRY) and β-caryophyllene oxide (CRYO) to inhibit the mutagenicity of CBE was studied as a possible preventive strategy. In order to identify the potential antimutagenic mechanisms, three different protocols (pretreatment, cotreatment, and posttreatment) were applied. CBE showed to increase the number of revertant colonies in all the strains tested in presence of S9, so resulting mutagenic. In the antimutagenicity assay, both CRY and CRYO significantly reduced the revertant colonies induced by CBE, although with different potency and specificity. For both sesquiterpenes, the antimutagenicity was strong in all experimental conditions, except for the cotreatment of CRY with CBE in WP2uvrA, which produced a moderate inhibition. Both desmutagenic and bioantimutagenic mechanisms seem to be involved in the antimutagenicity of the test substances. Taking into account the potential genotoxicity of cigarette butts, CRY and CRYO appear as possible further candidates as environmental decontaminants against this hazardous waste. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1319-1328, 2016.

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

“…However, the involvement of other direct or indirect genoprotective mechanisms cannot be excluded. Our results agree with previous evidence about the genoprotective properties of β-caryophyllene towards the DNA-damage induced by different environmental carcinogens [31,32] and pollutants [42,43]. The evidence that β-caryophyllene can act through both desmutagenic and bioantimutagenic mechanisms [95] also supports present results in cholangiocytes.…”

“…Furthermore, it produces cytoprotective effects by modulating oxidative stress, apoptosis and inflammation [38][39][40][41], through the interference with different inflammatory pathways, such as the inducible nitric oxide synthase (iNOS), tumor necrosis factor-alfa (TNF-α) and nuclear factor-κB (NF-κB) [37]. Also, it exhibited chemopreventive properties, such as genoprotective and antiproliferative ones, by inhibiting DNA damage and STAT3 (signal transducer and activator of transcription 3) activation induced by environmental pollutants [31,32,42,43] and through affecting multiple cascades involved in cancer growth [37,[44][45][46][47]. Similar properties have been also reported for the metabolite β-caryophyllene oxide [48,49].…”

“…In line with previous evidence about the chemosensitizing properties of caryophyllane sesquiterpenes [24][25][26]50], in the present study we evaluated the ability of β-caryophyllene to synergize doxorubicin ( Figure 1) in Mz-ChA-1 cholangiocarcinoma cells under both long-term and metronomic exposure schedules. Furthermore, being β-caryophyllene known to be protective in normal tissue against several toxicants [31,32,[38][39][40][41][42][43], its ability to reduce doxorubicin toxicity in H69 noncancerous cholangiocytes, under the same exposure schedules applied for the doxorubicin chemosensitization, was assessed too. This could represent an important goal to overcome the toxicity drawback of doxorubicin chemotherapy while maintaining its anticancer efficacy.…”

Potentiation of Low-Dose Doxorubicin Cytotoxicity by Affecting P-Glycoprotein through Caryophyllane Sesquiterpenes in HepG2 Cells: an in Vitro and in Silico Study

“…Accordingly, β-caryophyllene is known to bind to the CB2 receptor as an agonist and to induce anti-inflammatory, analgesic and neuroprotective effects [46][47][48]. Furthermore, both sesquiterpenes have been highlighted to possess interesting chemopreventing properties, due to their ability to counteract cell injury induced by environmental pollutants [49][50][51][52] and to inhibit cancer cell growth and proliferation, through affecting several key pathways for cancer development, such as mitogen-activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways [47,[53][54][55][56]. Also, they were reported to potentiate the efficacy of some anticancer drugs, acting as chemosensitizers [15][16][17]19,20].…”

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

“…These data indicated the peripheral analgesic and anti-inflammatory activity of caryophyllene oxide (Chavan, Wakte & Shinde, 2010). In addition, it has been reported to reduce the mutagenicity of commonly discharged cigarette butts (Di Giacomo, Mazzanti & Di Sotto, 2015). …”