β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

Rubini, Elisabetta; Paglia, Giuliano; Cannella, David; Macone, Alberto; Sotto, Antonella Di; Gullì, Marco; Altieri, Fabio; Eufemi, Margherita

doi:10.3390/biomedicines8110505

Cited by 19 publications

(19 citation statements)

References 38 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous cellular studies from our laboratory investigated β-HCH’s activity on a panel of different cancer cell lines with the purpose of clarifying its biological effects. The obtained results demonstrated the capability of β-HCH to promote tumor progression through several molecular processes, which include STAT3 canonical and non-canonical activation, endocrine disruption, Aryl Hydrocarbon Receptor activation, and modulation of redox homeostasis and energy metabolism [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Protein extraction and immunoblotting analysis were performed essentially according to Rubini et al [ 20 ]. Cells cultured on 6-well plates were scraped, harvested by centrifugation, and washed in PBS (Sigma Aldrich, cat.…”

Section: Methodsmentioning

confidence: 99%

“…Cellular studies carried out on a panel of cancer cell lines contributed to elucidating β-HCH’s activation pathways, identifying the protein STAT3 (Signal Transducer and Activator of Transcription 3) as the main modulator in the molecular responses induced by this organochlorine [ 19 ]. Further investigations shed some light on the potential activity of β-HCH as an endocrine-disrupting chemical, assessing its capability to activate AhR signaling and to promote other cellular functions related to redox homeostasis and energy metabolism [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Protein extraction and immunoblotting analysis were performed essentially according to Rubini et al [ 19 ]. Cells cultured on 6-well plates at a density of 300,000 cells/well, harvested by centrifugation, and washed in PBS (Sigma–Aldrich, Milano, Italy, cat.…”

Section: Methodsmentioning

confidence: 99%

“…Results from experiments, performed on a panel of different cell lines, demonstrated that the oncoprotein STAT3 (Signal Transducer and Activator of Transcription 3) is a converging point in the transduction pathways triggered by β-HCH and outlined the xenobiotic functions of this organochlorine, which is capable of impacting on the three stages of carcinogenesis [ 17 , 18 ]. In particular, β-HCH was proven to: foster cell proliferation and clonogenic potential, act as an endocrine disruptor via Aryl hydrocarbon Receptor and Androgen Receptor activation (AhR and AR), induce Reactive Oxygen Species (ROS) production and DNA damage, promote the metabolic rewiring toward aerobic glycolysis (Warburg Effect) and affect cell cycle progression [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

et al. 2021

Self Cite

View full text Add to dashboard Cite

The β-isomer of hexachlorocyclohexane (β-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of β-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating β-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting β-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from β-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

show abstract

Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

Donat-Vargas,

Schillemans,

Kiviranta

et al. 2023

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceCardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population.ObjectiveTo evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population.Design, Setting, and ParticipantsThis prospective nested case–control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023.ExposuresA total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography–triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included.Main Outcomes and MeasuresIncident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD.ResultsOf 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes.Conclusions and RelevanceIn this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.

show abstract

β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

Cited by 19 publications

References 38 publications

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

Contact Info

Product

Resources

About