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

Sep 24, 2026

Glutathione S-transferase P1 (GSTP1) expression increases in cancer cells and contributes to anticancer drug resistance. Chlorophyllin, an antioxidant, suppresses GSTP1 activity. This study evaluates chlorophyllin alone and in combination with docetaxel to understand effects on metastatic processes in triple-negative breast cancer. Using 4T1 cells and a metastatic animal model, viability, cell cycle, migration, gelatinase activity, GST activity, and glutathione levels were assessed, with histochemical micrometastasis evaluation in liver tissue.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Methods and experimental assays

Results and micrometastasis assessment

Conclusion

Naunyn-Schmiedeberg's Archives of Pharmacology (2025) 398:10569–10580 [https://doi.org/10.1007/s00210-025-03929-y](https://doi.org/10.1007/s00210-025-03929-y) The effect of the combination therapy with chlorophyllin, a glutathione transferase P1‑1 inhibitor, and docetaxel on triple‑negative breast cancer invasion and metastasis in vivo/in vitro Ayse Burus1 · Mehmet Ozcan2 · Hande Canpinar3 · Ozlem Bozdemir4 · Naciye Dilara Zeybek5 · Yasemin Bayazit1 Received: 7 January 2025 / Accepted: 13 February 2025 / Published online: 27 February 2025 © The Author(s) 2025 Abstract 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 effect 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. Total gelatinase activity, GST activity, and glutathione levels in cell and liver tissue lysates measured by colorimetric methods. Micrometastases were evaluated histochemically in liver tissue sections. As a result, the coadministration of chlorophyllin and docetaxel significantly inhibited cell migration in vitro. There was a significant decrease in the total gelatinase activity in vivo. We found that only combined treatment reduced the micrometastatic lesions in the liver tissues, though this reduction was not statistically significant. In conclusion, the coadministration of chlorophyllin and docetaxel may have a potential role in controlling metastatic processes by suppressing cell migration, gelatinase activity, and micrometastasis formation in triple-negative breast cancers. Keywords Triple negative breast cancer · Metastasis · Chlorophyllin · Antioxidants · Glutathione S-transferase · Combination therapy * Ayse Burus[ayseburus@hacettepe.edu.tr](ayseburus@hacettepe.edu.tr)[ ](ayseburus@hacettepe.edu.tr)Mehmet Ozcan [biochemistmozcan@gmail.com](biochemistmozcan@gmail.com)[ ](biochemistmozcan@gmail.com)Hande Canpinar [handecanpina@hacettepe.edu.tr](handecanpina@hacettepe.edu.tr)[ ](handecanpina@hacettepe.edu.tr)Ozlem Bozdemir [ozlembozdemir@hacettepe.edu.tr](ozlembozdemir@hacettepe.edu.tr)[ ](ozlembozdemir@hacettepe.edu.tr)Naciye Dilara Zeybek [dilaraz@hacettepe.edu.tr](dilaraz@hacettepe.edu.tr) Yasemin Bayazit [yaseminb@hacettepe.edu.tr](yaseminb@hacettepe.edu.tr) 1 Department of Medical Biochemistry, Hacettepe University Faculty of Medicine, Ankara, Turkey 2 Department of Medical Biochemistry, Zonguldak Bulent Ecevit University Faculty of Medicine, Zonguldak, Turkey 3 Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey 4 Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Ankara, Turkey 5 Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey Introduction With an increasing incidence, breast cancer has the most common cancer type in women accompanied by high mortality rates (Braithwaite et al. 2016) . In the treatment of breast cancer, different treatment options can be applied according to the subtypes of the disease. However, among these cancer subtypes, triple negative (ER- , PR − , and HER2- ) breast cancer without receptor sensitivity is the most lethal subtype due to its heterogeneity, aggressiveness, and lack of treatment options (Nedeljkovic and Damjanovic 2019) . Since there is no response to hormonal therapy or HER2-targeted drug therapies, chemotherapy remains one of the main treatment options, yet the prognosis remains poor due to high recurrence rates and drug resistance (Won and Spruck 2020 , An et al. 2021) . O

FAQs

Why is GSTP1 important in triple-negative breast cancer treatment resistance?

GSTP1 expression increases in cancer cells and contributes to anticancer drug resistance by promoting detoxification processes that reduce drug efficacy.

What was the experimental design used to study the drug effects?

The study used the 4T1 triple-negative breast cancer cell line and a metastatic animal model, assessing viability, cell cycle, migration, enzyme activities, and glutathione levels.

What impact did combining chlorophyllin with docetaxel have on metastasis-related outcomes?

Combined treatment significantly inhibited cell migration in vitro and decreased total gelatinase activity in vivo, and it reduced liver micrometastatic lesions without statistical significance.

Sep 24, 2026

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