ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic activity

Shang, Futai; Hui, Liangliang; An, Xizhong; Xiangcheng, Zhang; Guo, Shiguang; Zang, Kui

doi:10.1016/j.biopha.2015.03.005

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…In vivo studies, ZnPPIX reduced tumor growth of LL/2 lung cancer in C57BL mice, by suppressing vascular endothelial growth factor concentration in tumors [101]. In addition, ZnPPIX inhibited peritoneal metastasis of gastric cancer via anti-angiogenesis and improved the survival of tumor-bearing mice, which were related to the suppression of ROS production and ERK activation [102]. However, the non-selective activity of metalloporphyrin limits its application, due to the similarity of structure to heme.…”

Section: Ho-1 Modulators In Cancer Treatmentmentioning

confidence: 99%

A Dual Role of Heme Oxygenase-1 in Cancer Cells

Chiang

Chen

Chang

2018

IJMS

343

249

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Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.

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Section: Ho-1 Modulators In Cancer Treatmentmentioning

confidence: 99%

A Dual Role of Heme Oxygenase-1 in Cancer Cells

Chiang

Chen

Chang

2018

IJMS

343

249

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“…In colorectal cancer cells, HO-1 inhibition suppresses the expression of HIF-1α and VEGF and decreases the degree of angiogenesis in a mouse xenograft model [126]. In tumor-bearing mice, the use of ZnPPIX to inhibit HO-1 prevents peritoneal metastasis of gastric cancer by reducing angiogenesis [127]. In addition, as recently reported by Lin and coworkers, HO-1 expression in the tumor niche promotes lung metastasis by controlling VEGF and IL-10 production [122].…”

Section: Ho-1 In Invasiveness Angiogenesis and Metastatic Potentialmentioning

confidence: 99%

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

et al. 2017

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The upregulation of heme oxygenase-1 (HO-1) is one of the most important mechanisms of cell adaptation to stress. Indeed, the redox sensitive transcription factor Nrf2 is the pivotal regulator of HO-1 induction. Through the antioxidant, antiapoptotic, and antinflammatory properties of its metabolic products, HO-1 plays a key role in healthy cells in maintaining redox homeostasis and in preventing carcinogenesis. Nevertheless, several lines of evidence have highlighted the role of HO-1 in cancer progression and its expression correlates with tumor growth, aggressiveness, metastatic and angiogenetic potential, resistance to therapy, tumor escape, and poor prognosis, even though a tumor- and tissue-specific activity has been observed. In this review, we summarize the current literature regarding the pro-tumorigenic role of HO-1 dependent tumor progression as a promising target in anticancer strategy.

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“…Starting from the modulation of HO-1, the major effector of the pathway considered, several “in vivo” studies have confirmed the usefulness of the HO-1 competitive inhibitor zinc (II) protoporphyrin IX, ZnPPIX, in the reduction of hepatoma, sarcoma, lung cancer, and B-cell lymphoma growth in mice [ 129 , 171 ]. Moreover, the PEG conjugation of ZnPPIX, which increases water solubility of the inhibitor, is able to improve its clinical application [ 172 ].…”

Section: Pharmacological Modulation Of Nrf2/ho-1 Axis As a Strategmentioning

confidence: 99%

The Nrf2/HO‐1 Axis in Cancer Cell Growth and Chemoresistance

Furfaro

Traverso

Domenicotti

et al. 2015

Oxidative Medicine and Cellular Longevity

243

210

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The transcription factor, nuclear factor erythroid 2 p45-related factor 2 (Nrf2), acts as a sensor of oxidative or electrophilic stresses and plays a pivotal role in redox homeostasis. Oxidative or electrophilic agents cause a conformational change in the Nrf2 inhibitory protein Keap1 inducing the nuclear translocation of the transcription factor which, through its binding to the antioxidant/electrophilic response element (ARE/EpRE), regulates the expression of antioxidant and detoxifying genes such as heme oxygenase 1 (HO-1). Nrf2 and HO-1 are frequently upregulated in different types of tumours and correlate with tumour progression, aggressiveness, resistance to therapy, and poor prognosis. This review focuses on the Nrf2/HO-1 stress response mechanism as a promising target for anticancer treatment which is able to overcome resistance to therapies.

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ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic activity

Cited by 15 publications

References 16 publications

A Dual Role of Heme Oxygenase-1 in Cancer Cells

A Dual Role of Heme Oxygenase-1 in Cancer Cells

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

The Nrf2/HO‐1 Axis in Cancer Cell Growth and Chemoresistance

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