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Article ; Online: Is the mushroom Meripilus giganteus a potential cancer chemopreventive agent?

Lenzi, Monia / Gasperini, Sofia

2023 Volume 38, Issue 3, Page(s) 1170–1172

MeSH term(s)	Humans ; Agaricales ; Polyporales ; Neoplasms
Language	English
Publishing date	2023-04-22
Publishing country	England
Document type	Letter
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7856
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Article ; Online: Genotoxicity Evaluation of The Novel Psychoactive Substance MTTA.

Lenzi, Monia / Gasperini, Sofia / Corli, Giorgia / Marti, Matteo / Hrelia, Patrizia

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In ... ...

Abstract	MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test". To consider the in vitro effects of both the parental compound and the related metabolites, TK6 cells were treated with MTTA in the absence or presence of an exogenous metabolic activation system (S9 mix) for a short-term time (3 h) followed by a recovery period (23 h). No statistically significant increase in the MNi frequency was detected. Specifically, in the presence of S9 mix, only a slight increasing trend was observable at all tested concentrations, whereas, without S9 mix, at 75 µM, almost a doubling of the negative control was reached. For the purposes of comprehensive evaluation, a long-term treatment (26 h) was also included. In this case, a statistically significant enhancement in the MNi frequency was observed at 50 µM.
MeSH term(s)	Animals ; Micronucleus Tests/methods ; Mutagens/toxicity ; Mutagens/metabolism ; DNA Damage ; Central Nervous System Agents ; Mutagenicity Tests/methods ; Mammals/metabolism
Chemical Substances	Mutagens ; (5-methoxy-2-thienyl)thioacetic acid (58386-00-8) ; mephtetramine ; Central Nervous System Agents
Language	English
Publishing date	2023-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310498
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Article ; Online: Anthraquinones: Genotoxic until Proven Otherwise? A Study on a Substance-Based Medical Device to Implement Available Data for a Correct Risk Assessment.

Cocchi, Veronica / Gasperini, Sofia / Lenzi, Monia

Toxics

2022 Volume 10, Issue 3

Abstract: A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The "In Vitro Mammalian Cell Micronucleus Test" was performed on human TK6 cells by flow ... ...

Abstract	A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The "In Vitro Mammalian Cell Micronucleus Test" was performed on human TK6 cells by flow cytometry. Cultures were treated with concentrations of SMD tested in the range of 0-2 mg/mL for short treatment time (3 h) both in the absence and presence of an exogenous metabolic activation system, followed by a recovery period in fresh medium (23 h) and for extended treatment time (26 h) without an exogenous metabolic activation system. At the end of both treatment times, cytotoxicity, cytostasis, apoptosis and micronuclei (MNi) frequency were analysed in treated cultures and then compared with those measured in concurrent negative control cultures. The SMD did not induce a statistically significant increase MNi frequency under any of experimental conditions tested. The negative outcome shows that the SMD is non-mutagenic in terms of its ability to induce chromosomal aberrations both in the absence and presence of an exogenous metabolic activation system. The study ended by analyzing intracellular ROS levels to exclude the pro-oxidant ability, typically linked to DNA damage. On the contrary, our results demonstrated the ability the SMD to counteract oxidative stress.
Language	English
Publishing date	2022-03-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics10030142
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Article: Antimutagenicity and Antioxidant Activity of

Gasperini, Sofia / Greco, Giulia / Angelini, Sabrina / Hrelia, Patrizia / Fimognari, Carmela / Lenzi, Monia

Pharmaceutics

2023 Volume 15, Issue 10

Abstract: ... Castanea ... ...

Abstract	Castanea sativa
Language	English
Publishing date	2023-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15102465
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Article ; Online: 6-(Methylsulfonyl) Hexyl Isothiocyanate: A Chemopreventive Agent Inducing Autophagy in Leukemia Cell Lines.

Cocchi, Veronica / Jávega, Beatriz / Gasperini, Sofia / O'Connor, José-Enrique / Lenzi, Monia / Hrelia, Patrizia

Biomolecules

2022 Volume 12, Issue 10

Abstract: Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged ... ...

Abstract	Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles, and reactive oxygen species (ROS), while during the advanced stages of cancer, autophagy is exploited by cancer cells to survive under starvation. 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) is the most interesting compound in the Wasabia Japonica rizhome. Recently, we proved its ability to induce cytotoxic, cytostatic, and cell differentiation effects on leukemic cell lines and its antimutagenic activity on TK6 cells. In the current study, to further define its chemopreventive profile, Jurkat and HL-60 cells were treated with 6-MITC for 24 h. The modulation of the autophagic process and the involvement of ROS levels as a possible trigger mechanisms were analyzed by flow cytometry. We found that 6-MITC induced autophagy in Jurkat and HL-60 cells at the highest concentration tested and increased ROS intracellular levels in a dose-dependent manner. Our results implement available data to support 6-MITC as an attractive potential chemopreventive agent.
MeSH term(s)	Humans ; Reactive Oxygen Species ; Cytostatic Agents/pharmacology ; Isothiocyanates/pharmacology ; Leukemia/drug therapy ; Autophagy ; HL-60 Cells ; Apoptosis ; Cell Line, Tumor
Chemical Substances	6-(Methylsulfinyl)hexyl isothiocyanate ; Reactive Oxygen Species ; Cytostatic Agents ; isothiocyanic acid (3129-90-6) ; Isothiocyanates
Language	English
Publishing date	2022-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101485
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Article ; Online: The Genotoxicity of Acrylfentanyl, Ocfentanyl and Furanylfentanyl Raises the Concern of Long-Term Consequences.

Gasperini, Sofia / Bilel, Sabrine / Cocchi, Veronica / Marti, Matteo / Lenzi, Monia / Hrelia, Patrizia

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). ... ...

Abstract	Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property. The ability to induce structural and numerical chromosomal aberrations in human lymphoblastoid TK6 cells was evaluated by employing the flow cytometric protocol of the in vitro mammalian cell micronucleus test. Our study demonstrated the non-genotoxicity of Fentanyl, i.e., the pharmaceutical progenitor of the class, while its illicit non-pharmaceutical analogues were found to be genotoxic. In particular, Acrylfentanyl led to a statistically significant increase in the MNi frequency at the highest concentration tested (75 μM), while Ocfentanyl and Furanylfentnyl each did so at both concentrations tested (150, 200 μM and 25, 50 μM, respectively). The study ended by investigating reactive oxygen species (ROS) induction as a possible mechanism linked to the proved genotoxic effect. The results showed a non-statistically significant increase in ROS levels in the cultures treated with all molecules under study. Overall, the proved genotoxicity raises concern about the possibility of serious long-term consequences.
MeSH term(s)	Humans ; Reactive Oxygen Species ; Fentanyl/toxicity ; DNA Damage
Chemical Substances	acrylfentanyl (T64K7YD33B) ; furanyl fentanyl (3F7C9J1LS7) ; Reactive Oxygen Species ; Fentanyl (UF599785JZ)
Language	English
Publishing date	2022-11-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232214406
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Article ; Online: Genotoxicological Characterization of (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and Their Association.

Lenzi, Monia / Gasperini, Sofia / Cocchi, Veronica / Tirri, Micaela / Marti, Matteo / Hrelia, Patrizia

International journal of molecular sciences

2022 Volume 23, Issue 10

Abstract: The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still ... ...

Abstract	The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the "In Vitro Mammalian Cell Micronucleus Test" (MNvit) on (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates' opposite behaviours: (±)cis-4,4'-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (±)trans-4,4'-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition.
MeSH term(s)	Animals ; Central Nervous System Stimulants/pharmacology ; Humans ; Illicit Drugs/pharmacology ; Isomerism ; Mammals ; Oxazoles/pharmacology
Chemical Substances	Central Nervous System Stimulants ; Illicit Drugs ; Oxazoles ; para-methyl-4-methylaminorex (18Y239214S)
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23105849
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Article ; Online: Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP.

Lenzi, Monia / Cocchi, Veronica / Gasperini, Sofia / Arfè, Raffaella / Marti, Matteo / Hrelia, Patrizia

International journal of molecular sciences

2021 Volume 22, Issue 12

Abstract: Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present ... ...

Abstract	Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35-100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.
MeSH term(s)	Alkaloids/toxicity ; Apoptosis/drug effects ; Cell Death/drug effects ; Cell Line ; Cell Survival/drug effects ; Humans ; Methamphetamine/analogs & derivatives ; Methamphetamine/toxicity ; Micronucleus, Germline/drug effects ; Micronucleus, Germline/metabolism ; Mutagens/toxicity ; Pentanones/toxicity ; Pyrrolidines/toxicity ; Reactive Oxygen Species/metabolism
Chemical Substances	Alkaloids ; Mutagens ; Pentanones ; Pyrrolidines ; Reactive Oxygen Species ; alpha-pyrrolidinohexanophenone ; mexedrone ; Methamphetamine (44RAL3456C) ; cathinone (540EI4406J) ; 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (767K3AWA4R)
Language	English
Publishing date	2021-06-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22126320
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Article ; Online: Novel Psychoactive Phenethylamines: Impact on Genetic Material.

Cocchi, Veronica / Gasperini, Sofia / Hrelia, Patrizia / Tirri, Micaela / Marti, Matteo / Lenzi, Monia

International journal of molecular sciences

2020 Volume 21, Issue 24

Abstract: Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in ... ...

Abstract	Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and the popular 3,4-Methylenedioxymethylamphetamine (MDMA). On the basis of cytotoxicity and cytostasis results, we selected the concentrations (6.25-35 µM) to be used in genotoxicity analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by an automated flow cytometric protocol. All substances, except MDMA, resulted genotoxic; therefore, we evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the demonstrated genotoxicity. The obtained results showed a statistically significant increase in ROS levels for all genotoxic phenethylamines confirming this hypothesis. Our results highlight the importance of genotoxicity evaluation for a complete assessment of the risk associated also with NPS exposure. Indeed, the subjects who do not have hazardous behaviors or require hospitalization by using active but still "safe" doses could run into genotoxicity and in the well-known long-term effects associated.
MeSH term(s)	Anisoles/pharmacology ; Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; Dimethoxyphenylethylamine/analogs & derivatives ; Dimethoxyphenylethylamine/pharmacology ; Flow Cytometry/methods ; Genes/drug effects ; Hallucinogens/pharmacology ; Humans ; Micronuclei, Chromosome-Defective/chemically induced ; Micronucleus Tests/methods ; N-Methyl-3,4-methylenedioxyamphetamine/pharmacology ; Phenethylamines/pharmacology ; Psychotropic Drugs/pharmacology ; Reactive Oxygen Species/analysis ; Reactive Oxygen Species/metabolism
Chemical Substances	Anisoles ; Dimethoxyphenylethylamine ; Hallucinogens ; Phenethylamines ; Psychotropic Drugs ; Reactive Oxygen Species ; N-Methyl-3,4-methylenedioxyamphetamine (KE1SEN21RM) ; 4-iodo-2,5-dimethoxy-beta-phenethylamine (S35362848V) ; 2-(4-bromo-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine (S6NAA81PHK) ; 2-(4-bromo-2,5-dimethoxyphenyl)ethylamine (V77772N32H)
Language	English
Publishing date	2020-12-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21249616
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Article: In Vitro Investigation of the Anticancer Properties of Ammodaucus Leucotrichus

Lenzi, Monia / Turrini, Eleonora / Catanzaro, Elena / Cocchi, Veronica / Guerrini, Alessandra / Hrelia, Patrizia / Gasperini, Sofia / Stefanelli, Claudio / Abdi Bellau, Mohamed Lamin / Pellicioni, Valentina / Tacchini, Massimo / Greco, Giulia / Fimognari, Carmela

Pharmaceuticals (Basel, Switzerland)

2022 Volume 15, Issue 12

Abstract: Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. ...

Abstract	Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy.
Language	English
Publishing date	2022-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph15121491
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