Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1‐1 inhibitor, in tumorigenesis and tumor progression

Özcan, Mehmet; Esendağlı, Güneş; Musdal, Yaman; Canpınar, Hande; Bacanlı, Merve; Anlar, Hatice Gül; Esendagli-Yilmaz, Guldal; Beyramzadeh, Mojtaba; Aksoy, Yasemin

doi:10.1002/jcb.27974

Cited by 13 publications

(8 citation statements)

References 41 publications

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Section: Antioxidant Capacity Of Chlorophyllsmentioning

confidence: 99%

“…Chlorophyllin enhanced the nuclear translocation of Nrf-2 in mouse splenic lymphocytes in both a dose-and time-dependent manner [201]. In rats with breast cancer, chlorophyllin increased the GSH levels in the liver [202]. Another line of research comes from the assumption that chlorophyll a and its derivatives have been proposed to exert antidiabetic functions [203].…”

Section: In Vivo Activation Of Detoxification Pathways By Chlorophyllsmentioning

confidence: 99%

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Carotenoids and Chlorophylls as Antioxidants

2020

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Chlorophylls and carotenoids are natural pigments that are present in our daily diet, especially with the increasing tendency towards more natural and healthy behaviors among consumers. As disturbed antioxidant homeostasis capacities seem to be implicated in the progress of different pathologies, the antioxidant properties of both groups of lipophilic compounds have been studied. The objective of this review was to analyze the state-of-the-art advances in this field. We conducted a systematic bibliographic search (Web of Science™ and Scopus®), followed by a comprehensive and critical description of the results, with special emphasis on highly cited and more recently published research. In addition to an evaluative description of the methodologies, this review discussed different approaches used to obtain a physiological perspective, from in vitro studies to in vivo assays using oxidative biomarkers. From a chemical viewpoint, many studies have demonstrated how a pigment’s structure influences its antioxidant response and the underlying mechanisms. The major outcome is that this knowledge is essential for interpreting new data in a metabolic networks context in the search for more direct applications to health. A promising era is coming where the term “antioxidant” is understood in terms of its broadest significance.

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Section: Antioxidant Capacity Of Chlorophyllsmentioning

confidence: 99%

Section: In Vivo Activation Of Detoxification Pathways By Chlorophyllsmentioning

confidence: 99%

Carotenoids and Chlorophylls as Antioxidants

2020

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“…For instance, the activation of signaling pathways containing TGFβ, WNT, NOTCH, MYC, and EMT-related genes occur only late during hepatocarcinogenesis and they affect oncogenic driver genes for cell survival, angiogenesis, and treatment resistance. [38][39][40]…”

Section: Potential Therapies Through Targeting Driver Genes and Key Pathwaysmentioning

confidence: 99%

Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach

et al. 2020

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death primarily due to the lack of effective targeted therapies. Despite the distinct morphological and phenotypic patterns of HCC, treatment strategies are restricted to relatively homogeneous therapies, including multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors. Therefore, more effective therapy options are needed to target dysregulated metabolic and molecular pathways in HCC. Integrative genomic profiling of HCC patients provides insight into the most frequently mutated genes and molecular targets, including telomerase reverse transcriptase, the TP53 gene, and the Wnt/β‐catenin signaling pathway oncogene (CTNNB1). Moreover, emerging techniques, such as genome‐scale metabolic models may elucidate the underlying cancer‐specific metabolism, which allows for the discovery of potential drug targets and identification of biomarkers. De novo lipogenesis has been revealed as consistently upregulated since it is required for cell proliferation in all HCC patients. The metabolic network‐driven stratification of HCC patients in terms of redox responses, utilization of metabolites, and subtype‐specific pathways may have clinical implications to drive the development of personalized medicine. In this review, the current and emerging therapeutic targets in light of molecular approaches and metabolic network‐based strategies are summarized, prompting effective treatment of HCC patients.

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“…Chlorophyllin was shown to be a speci c inhibitor of GSTP1. In a previous study of our group, it was demonstrated that chlorophyllin had a suppressing effect on the spread of breast cancer in an animal model chemically induced with N-methyl nitrosourea (Ozcan, Esendagli et al 2018). However, in this study, the e cacy of chlorophyllin administration on breast cancer-induced liver metastasis was investigated, and it was revealed that chlorophyllin might have inhibitory effects on metastasis by reducing migration, MMP expression, and enzyme activity.…”

Section: Discussionmentioning

confidence: 80%

The effect of chlorophyllin, a glutathione transferase P1‐1 inhibitor, on triple-negative breast cancer invasion and metastasis in vivo/in vitro

burus,

Ozcan,

Canpinar

et al. 2024

Preprint

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The expression of glutathione S-transferase P1 (GSTP1) enzyme increases in cancer cells, leading to anticancer drug resistance. The antioxidant chlorophyllin has an inhibitory effect on GSTP1. In this study, we investigated the effects of chlorophyllin and its combined administration with the chemotherapeutic agent docetaxel on metastatic processes. For this purpose, both the 4T1 triple-negative breast cancer cell line and metastatic animal model were used. The MTT, flow cytometry, and wound healing assays were used to investigate cell viability, cell cycle, and cell migration, respectively. Western blot analysis was used to evaluate the expression of matrix metalloproteinase 9 (MMP-9). Total gelatinase activity, GST activity, and glutathione levels in cell and liver tissue lysates measured by colorimetric methods. Micrometastases were evaluated in liver tissue sections histochemically. As a result, the coadministration of chlorophyllin and docetaxel inhibited cell migration in vitro. The single administration of chlorophyllin reduced the MMP-9 expression in vivo, and this effect was higher when it was coadministered with docetaxel. In coadministration, there was also a significant decrease in the total gelatinase activity in vivo. Finally, we found that only combined treatment reduced the micrometastatic lesions in the liver tissues. In conclusion, the coadministration of chlorophyllin and docetaxel may have a potential role in the control of metastatic processes by suppressing cell migration, invasion, and micrometastasis formation in triple-negative breast cancers.

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Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1‐1 inhibitor, in tumorigenesis and tumor progression

Cited by 13 publications

References 41 publications

Carotenoids and Chlorophylls as Antioxidants

Carotenoids and Chlorophylls as Antioxidants

Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach

The effect of chlorophyllin, a glutathione transferase P1‐1 inhibitor, on triple-negative breast cancer invasion and metastasis in vivo/in vitro

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