Targeting Obesity-Associated Breast Cancer: Curcumin Counteracts Leptin-Induced Tumorigenic and Metastatic Traits in MCF-7 and MDA-MB-231 Breast Cancer Cells.
- 1Laboratory of Genetics, Immunology, and Human Pathologies, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis 1068, Tunisia.
- 2Laboratoire de Biologie Intégrative pour l'Innovation Thérapeutique (BioInov), Faculté des Sciences et Techniques (FAST), Université d'Abomey-Calavi, Abomey-Calavi BP 526, Benin.
- 3Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410105, Nigeria.
Abstract
Obesity-driven hyperleptinemia is a key driver of breast cancer (BC) aggressiveness; nevertheless, strategies to counteract leptin-mediated tumor progression remain limited. Curcumin, a natural polyphenol with established anti-obesity, anti-inflammatory, and anticancer properties, has emerged as a promising metabolic and tumor-modulating biomolecule, although its effects on leptin-induced oncogenic signaling remain unclear. This study evaluated Curcumin as an adjuvant nutraceutical against leptin-induced oncogenesis in MCF-7 and MDA-MB-231 cells. Cells were exposed to obesity-mimicking leptin levels alone or with non-toxic Curcumin doses. MTT, clonogenic, wound-healing, and 3D spheroid dissemination assays were used to assess phenotypic changes, while network pharmacology and molecular docking explored underlying mechanisms. Curcumin significantly inhibited leptin-induced proliferation (8-17%), colony formation (60-90%), migration (20-45%), and 3D spheroid dissemination (20%) in both BC cell lines. Network pharmacology identified shared hub proteins, including AKT1, RHOA, MAP2K1, and MAPK14, linking Curcumin targets with leptin-driven BC signatures, and molecular docking supported direct interactions of Curcumin with these proteins. These findings suggest that Curcumin counteracts hyperleptinemia-induced tumor progression by targeting the PI3K/AKT, MAPK/ERK, and RHOA/ROCK pathways. This integrated in vitro and in silico study supports Curcumin as a promising adjuvant nutraceutical for obesity-associated BC, although experimental pathway validation is still required.
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BibTeX
@article{attia2026targeting,
title = {{Targeting Obesity-Associated Breast Cancer: Curcumin Counteracts Leptin-Induced Tumorigenic and Metastatic Traits in MCF-7 and MDA-MB-231 Breast Cancer Cells.}},
author = {Hanène Attia and Orace Mathieu Kenou and Khouloud Ayed and Stanley Arinze Abonyi and Rym Akrout and Rahma Boughriba and Ali Ben Cheikh and Sylvère Fidèle Fassinou and Tomabu Adjobimey and Wassim Y Almawi and Asma Gati},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198572},
url = {https://europepmc.org/article/MED/42883819},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting Obesity-Associated Breast Cancer: Curcumin Counteracts Leptin-Induced Tumorigenic and Metastatic Traits in MCF-7 and MDA-MB-231 Breast Cancer Cells.
AU - Hanène Attia
AU - Orace Mathieu Kenou
AU - Khouloud Ayed
AU - Stanley Arinze Abonyi
AU - Rym Akrout
AU - Rahma Boughriba
AU - Ali Ben Cheikh
AU - Sylvère Fidèle Fassinou
AU - Tomabu Adjobimey
AU - Wassim Y Almawi
AU - Asma Gati
PY - 2026
DA - 2026/09/25
JO - International journal of molecular sciences
DO - 10.3390/ijms27198572
UR - https://europepmc.org/article/MED/42883819
AB - Obesity-driven hyperleptinemia is a key driver of breast cancer (BC) aggressiveness; nevertheless, strategies to counteract leptin-mediated tumor progression remain limited. Curcumin, a natural polyphenol with established anti-obesity, anti-inflammatory, and anticancer properties, has emerged as a promising metabolic and tumor-modulating biomolecule, although its effects on leptin-induced oncogenic signaling remain unclear. This study evaluated Curcumin as an adjuvant nutraceutical against leptin-induced oncogenesis in MCF-7 and MDA-MB-231 cells. Cells were exposed to obesity-mimicking leptin levels alone or with non-toxic Curcumin doses. MTT, clonogenic, wound-healing, and 3D spheroid dissemination assays were used to assess phenotypic changes, while network pharmacology and molecular docking explored underlying mechanisms. Curcumin significantly inhibited leptin-induced proliferation (8-17%), colony formation (60-90%), migration (20-45%), and 3D spheroid dissemination (20%) in both BC cell lines. Network pharmacology identified shared hub proteins, including AKT1, RHOA, MAP2K1, and MAPK14, linking Curcumin targets with leptin-driven BC signatures, and molecular docking supported direct interactions of Curcumin with these proteins. These findings suggest that Curcumin counteracts hyperleptinemia-induced tumor progression by targeting the PI3K/AKT, MAPK/ERK, and RHOA/ROCK pathways. This integrated in vitro and in silico study supports Curcumin as a promising adjuvant nutraceutical for obesity-associated BC, although experimental pathway validation is still required.
SN - 1422-0067
ER -