Arsenic compounds: The wide application and mechanisms applied in acute promyelocytic leukemia and carcinogenic toxicology

Liu, Guangzhi; Song, Yurong; Li, Chenxi; Li, Rui; Chen, Youwen; Yu, Liuchunyang; Huang, Qingcai; Zhu, Dongjie; Lü, Cheng; Yu, Xue; Xiao, Cheng; Liu, Yuanyan

doi:10.1016/j.ejmech.2021.113519

Cited by 22 publications

(13 citation statements)

References 117 publications

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“…ATO directly binds with PML-RARα and enhances product degradation via the ubiquitin-proteasome system, thereby promoting differentiation of APL cells ( 59 ). ATO also induces mitochondria-dependent apoptosis of APL cells through inhibition of glutathione peroxidase and the c-Myc–targeted gene, peroxiredoxin III ( 60 ). Further, the efficacy of single-agent ATO treatment has been evaluated in a range of solid tumor types including hepatic, esophageal, gastric, pancreatic, ovarian, and prostatic carcinomas ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling

Hsieh¹,

Lin²,

Huang³

et al. 2022

JCI Insight

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Docetaxel (DTX) combined with cisplatin and 5-FU has been used as induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). However, the development of acquired resistance remains a major obstacle to treatment response. Tumor-associated macrophages are associated with chemotherapeutic resistance. In the present study, increased infiltration of macrophages into the tumor microenvironment was significantly associated with shorter overall survival and increased resistance to chemotherapeutic drugs, particularly DTX in HNSCC patients. Macrophage co-culture induced expression of intercellular adhesion molecule 1 (ICAM1), which promotes stemness and the formation of polyploid giant cancer cells, thereby reducing the efficacy of DTX. Both genetic silencing and pharmacological inhibition of ICAM1 sensitized HNSCC to DTX. Macrophage secretion of IL-1β was found to induce tumor expression of ICAM1. IL-1β neutralization and IL-1 receptor blockade reversed DTX resistance induced by macrophage co-culture. IL-1β activated superoxide dismutase 2 and inhibited catalase, thereby modulating intracellular levels of reactive oxygen species (ROS) and inducing ICAM1 expression. Arsenic trioxide (ATO) reduced macrophage infiltration into the TME and impaired IL-1β secretion by macrophages. The combinatorial use of ATO enhanced the in vivo efficacy of DTX in a mouse model, which may provide a revolutionary approach to overcoming acquired therapeutic resistance in HNSCC.Keywords: head and neck squamous cell carcinoma (HNSCC), docetaxel (DTX), tumor associated macrophage (TAM), IL-1β, intercellular adhesion molecule 1 (ICAM1), arsenic trioxide (ATO).

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Section: Discussionmentioning

confidence: 99%

Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling

Hsieh¹,

Lin²,

Huang³

et al. 2022

JCI Insight

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“…KRAS mutant lung cancer remains to find effective therapeutic treatment. Realgar has demonstrated an optimal anticancer effect ( 49 , 50 ). One of the main goals of the present study was to assess the effect of this compound on lung cancer cells with KRAS mutations.…”

Section: Discussionmentioning

confidence: 99%

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

et al. 2022

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KRAS is a biomarker for non-small cell lung cancer-targeted therapy, but there is currently no effective KRAS-targeting medication. Realgar is an impelling anticancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC 50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non-KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe 2+ , reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer-1. Realgar decreased phosphorylated p-Raf, p-ERK1/2 and increased p-p38 and p-JNK, whereas only p-Raf was abolished by Fer-1. Raf inhibitor Sorafenib accelerated the realgar-induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti-KRAS mutant lung cancer.

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“…Even methylated arsenicals, formerly thought to be harmless, can induce chromosome aberrations and are potent DNA-damaging agents (57). Arsenic and arsenic-containing compounds can activate or indirectly cause genetic changes or damage (58)(59)(60).…”

Section: Mechanism Of Genotoxicitymentioning

confidence: 99%

Metabolic and genetic derangement: a review of mechanisms involved in arsenic and lead toxicity and genotoxicity

Rodríguez-Seijo

2022

Archives of Industrial Hygiene and Toxicology

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Urbanisation and industrialisation are on the rise all over the world. Environmental contaminants such as potentially toxic elements (PTEs) are directly linked with both phenomena. Two PTEs that raise greatest concern are arsenic (As) and lead (Pb) as soil and drinking water contaminants, whether they are naturally occurring or the consequence of human activities. Both elements are potential carcinogens. This paper reviews the mechanisms by which As and Pb impair metabolic processes and cause genetic damage in humans. Despite efforts to ban or limit their use, due to high persistence both continue to pose a risk to human health, which justifies the need for further toxicological research.

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Arsenic compounds: The wide application and mechanisms applied in acute promyelocytic leukemia and carcinogenic toxicology

Cited by 22 publications

References 117 publications

Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling

Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

Metabolic and genetic derangement: a review of mechanisms involved in arsenic and lead toxicity and genotoxicity

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