Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

Castronuovo, Cynthia Celeste; Sacca, Paula Alejandra; Meiss, Roberto P.; Caballero, Fabiana; Batlle, Alcira; Vázquez, Elba S.

doi:10.1186/1471-2407-6-286

Cited by 5 publications

(4 citation statements)

References 32 publications

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“…Similarly, cleavage products of cytosolic HO‐1 can be translocated to the nucleus to regulate transcriptional activity 67. Indeed, one study correlated nuclear HO‐1 localization with PCA progression 68. Therefore, cooperation between HO‐1 and PTEN for castration resistance can occur at various levels.…”

Section: Discussionmentioning

confidence: 99%

PTEN deletion and heme oxygenase‐1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

Shi

Xiao

et al. 2011

The Journal of Pathology

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Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA.

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Section: Discussionmentioning

confidence: 99%

PTEN deletion and heme oxygenase‐1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

Shi

Xiao

et al. 2011

The Journal of Pathology

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“…It plays an important role in the modulation of inflammation, blocking the apoptotic process and antioxidant defense in the presence of any damage [ 20 , 21 ]. This enzyme is overexpressed in pancreatic, colon, and lung cancer, in which it can promote tumor cell proliferation and resistance to tumor therapy [ 22 , 23 ]. Induction of HO-1 in tumor cells undergoing any stressor agent increases their resistance to apoptosis [ 24 - 26 ].…”

Section: Introductionmentioning

confidence: 99%

Increase of IFN-γ and TNF-γ production in CD107a + NK-92 cells co-cultured with cervical cancer cell lines pre-treated with the HO-1 inhibitor

et al. 2014

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BackgroundNatural killer (NK) cells eliminate virus-infected and tumor cells through the release of perforins and granzymes; they also produce Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α), which induce apoptosis in target cells. Many tumors express Heme oxygenase 1 (HO-1), and this expression has been associated with avoiding immunosuppression and apoptosis. In this work, HO-1+ Cervical cancer cell (CCC) lines were pre-treated with HO-1 inhibitor and we assessed whether this inhibition enhanced the sensitivity of CCC to NK cell activity.MethodsWe assessed the expression of HO-1 in HeLa, SiHa, and C-33A CCC by Flow cytometry (FC). CCC were pre-treated with SnPP or ZnPP HO-1 inhibitors. After that, NK-92 cells were co-cultured with HeLa, SiHa, and C-33A CCC pre-treated or not with HO-1 inhibitors, and the expression of IFN-γ, TNF-α, CD107a, Granzyme B, NKp44, NKp46, NKp30, and NKG2D was evaluated by FC.ResultsCCC lines HeLa, SiHa, and C-33A expressed HO-1. Inhibition of HO-1 in these cells increased the expression of IFN-γ and TNF-α in CD107a + NK-92 cells. We observed a reduction in the expression of NKG2D, NKp46, and NKp30 in NK cells co-cultured with HeLa and SiHa cells, and when HeLa and SiHa cells were pre-treated with the HO-1 inhibitors, the expression of NKG2D and NKp30 in NK cells was restored. We observed a similar effect in NK cells co-cultured with C-33A cells in NKp30 expression.ConclusionInhibition of HO-1 in CCC induces an increase in IFN-γ and TNF-α production in CD107a + NK-92 cells and restores NKG2D, NKp46 and NKp30 downmodulation in NK cells.

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“…Tiene un papel importante en la modulación de procesos inflamatorios y en los mecanismos de defensa antioxidante que posee el organismo ante la presencia de algún daño y en el bloqueo de los procesos apoptóticos 15,16 . Esta enzima es sobreexpresada en cáncer de páncreas, colon y pulmón, en donde favorece la proliferación tumoral y resistencia a la terapia antitumoral 17,18 . La inducción de HO-1 en células tumorales, sometidas a algún agente estresor, incrementa su resistencia a la apoptosis.…”

Section: Introductionunclassified

Regulación de hemooxigenasa e indoleamina por citocinas en células de cáncer cervicouterino y actividad citotóxica de células natural killer

Ortiz‐Lazareno¹,

Lomeli²,

Flores³

et al. 2022

GAMO

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Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

Cited by 5 publications

References 32 publications

PTEN deletion and heme oxygenase‐1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

PTEN deletion and heme oxygenase‐1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

Increase of IFN-γ and TNF-γ production in CD107a + NK-92 cells co-cultured with cervical cancer cell lines pre-treated with the HO-1 inhibitor

Regulación de hemooxigenasa e indoleamina por citocinas en células de cáncer cervicouterino y actividad citotóxica de células natural killer

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