Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer

Abstract

Oxidative stresses (OSs) are considered a pivotal factor in creating various pathophysiological conditions. Cells have been able to move forward by modulating numerous signaling pathways to moderate the defects of these stresses during their evolution. The company of Kelch-like ECH-associated protein 1 (Keap1) as a molecular sensing element of the oxidative and electrophilic stress and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) as a master transcriptional regulator of the antioxidant response makes a master cytoprotective antioxidant pathway known as the Keap1/Nrf2 pathway. This pathway is considered a dual-edged sword with beneficial features for both normal and cancer cells by regulating the gene expression of the array of endogenous antioxidant enzymes. Heme oxygenase-1 (HO-1), a critical enzyme in toxic heme removal, is one of the clear state indicators for the duality of this pathway. Therefore, Nrf2/HO-1 axis targeting is known as a novel strategy for cancer treatment. In this review, the molecular mechanism of action of natural antioxidants on lung cancer cells has been investigated by relying on the Nrf2/HO-1 axis.

Icariin‑curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO‑1 signaling

“…Targeting the Nrf2/HO-1 axis has been introduced as a revolutionary cancer therapy ( 52 ). Nrf2 is a fundamental transcription factor that governs endogenous antioxidants, including HO-1( 53 ).…”

Câncer de Cabeça e Pescoço

“…A via KEAP1-NRF2 é composta por duas proteínas que interagem entre si, de modo a induzir a produção de antioxidantes endógenos quando diante de Outra via importante no CP está diretamente associada com a proteína NRF2. Dentre os genes transcritos por tal proteína, está o da enzima Heme oxigenase-1 (HO-1), responsável pelo catabolismo da heme em biliverdina, monóxido de carbono e ferro (GHAREGHOMI et al, 2023). Os produtos do catabolismo da heme em biliverdina possuem funções antioxidantes, anti-inflamatórias e antiapoptóticas, tendo assim forte ação de sobrevivência celular.…”

“…Em células neoplásicas, frequentemente em CP, essa enzima encontra-se super expressa devido mutações em seu gene, estando associada à resistência à quimioterapia e à radioterapia (GHAREGHOMI et al, 2023).…”

“…Além do supracitado, mutações em HO-1 estão correlacionadas à sobrevivência, proliferação, angiogênese e metástase celular. Devido à grande ação pró-oncótica que essa via possui, quando mutada, ela se torna uma possível estratégia terapêutica de grande importância no CP (GHAREGHOMI et al, 2023). Além disso, um importante recorte de gênero pode ser observado na incidência do câncer de tireoide, com a maioria dos casos, 83,4%, ocorrendo no sexo feminino, exibindo uma razão entre os sexos (F/M) de 5:1, estando assim entre as poucas neoplasias com dominância feminina de casos.…”

AMPK-Mediated Phosphorylation of Nrf2 at S374/S408/S433 Favors Its βTrCP2-Mediated Degradation in KEAP1-Deficient Cells

“…KEAP1 mutations are present in various pathological conditions, including neurological and metabolic disorders, cardiovascular diseases, and cancer [ 8 , 28 , 30 , 31 , 32 , 33 ], with a high prevalence in lung and pancreatic cancer [ 34 , 35 ]. These cancers then show hijacked NRF2 hyperactivation, which facilitates high tumor growth, therapy resistance, and metastasis [ 33 , 36 , 37 , 38 ] due to persistent antioxidant [ 39 ] and detoxification pathways [ 40 ], allowing cancer cells to fight stress induced by aberrant proliferation and therapy [ 38 , 41 ].…”