Crosstalk between aryl hydrocarbon receptor (AhR) and BCL-2 pathways suggests the use of AhR antagonist to maintain normal differentiation state of mammary epithelial cells during BCL-2 inhibition therapy

Al‐Dhfyan, Abdullah; Alaiya, Abdulkareem; Almohanna, Falah; Attwa, Mohamed W.; Alasmari, Abdullah F.; Bakheet, Saleh A.; Korashy, Hesham M.

doi:10.1016/j.jare.2022.10.006

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…In the present study, when HCB was administered alone, it did not modify cell viability or proliferation. However, several authors have described that AhR activation reduces the sensitivity to different antitumor therapies [61][62][63]. Specifically concerning chemotherapy, Goode et al [64] established the importance of AhR as modulators of the response, since these authors described that the knockout of this receptor in human breast tumor cells increased the sensitivity to a subsequent PX treatment.…”

Section: Discussionmentioning

confidence: 99%

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

Sanchez,

Vasquez Callejas,

Miret

et al. 2024

Exploration of Targeted Anti-Tumor Therapy

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Aim: Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells. Methods: Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot. Results: Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment. Conclusions: The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.

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Section: Discussionmentioning

confidence: 99%

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

Sanchez,

Vasquez Callejas,

Miret

et al. 2024

Exploration of Targeted Anti-Tumor Therapy

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Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development

Rayan,

Sayed,

Hussein

et al. 2024

Cell Mol Biol Lett

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Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients. The gut microbiome has recently been reported to interact with environmental factors such as diet and exposure to environmental toxicants. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) induces a shift in the gut microbiome metabolic pathways, favoring a proinflammatory microenvironment. In addition, other studies have also correlated cancer incidence with exposure to PAHs. PAHs are known to induce organ carcinogenesis through activating a ligand-activated transcriptional factor termed the aryl hydrocarbon receptor (AhR), which metabolizes PAHs to highly reactive carcinogenic intermediates. However, the crosstalk between AhR and the microbiome in mediating carcinogenesis is poorly reviewed. This review aims to discuss the role of exposure to environmental pollutants and activation of AhR on microbiome-associated cancer progression and explore the underlying molecular mechanisms involved in cancer development.

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Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities

Rahmati,

Moghtaderi,

Mohammadi

et al. 2024

World J Exp Med

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Esophageal squamous cell carcinoma (ESCC) is a substantial global health burden. Immune escape mechanisms are important in ESCC progression, enabling cancer cells to escape the surveillance of the host immune system. One key player in this process is the Aryl Hydrocarbon Receptor (AhR), which influences multiple cellular processes, including proliferation, differentiation, metabolism, and immune regulation. Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis, epithelial-mesenchymal transition, and immune escape. Targeting AhR signaling is a potential therapeutic approach for ESCC, with AhR ligands showing efficacy in preclinical studies. Additionally, modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention. This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

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Crosstalk between aryl hydrocarbon receptor (AhR) and BCL-2 pathways suggests the use of AhR antagonist to maintain normal differentiation state of mammary epithelial cells during BCL-2 inhibition therapy

Cited by 3 publications

References 35 publications

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development

Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities

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