Evaluation of the Effects of Plant Tinctures on Giant Polyploid Cancer Cells in Breast Cancer.

Name: ISABELE PAGANI PAVAN

Publication date: 23/07/2026

Examining board:

Namesort descending Role
DEBORA DUMMER MEIRA Coorientador
FLAVIA DE PAULA Examinador Interno
IURI DRUMOND LOURO Presidente
NATHALIA DE OLIVEIRA MEIRELES DA COSTA Examinador Externo

Summary: Breast cancer is the most prevalent malignancy among women and remains a major public health challenge due to its high tumor heterogeneity and the development of resistance to conventional therapies. Among the mechanisms underlying this process,
Polyploid Giant Cancer Cells/Multinucleated Giant Cancer Cells (PGCCs/MNGCs) have emerged as highly plastic cellular subpopulations associated with stress adaptation, tumor recurrence, and disease progression. In this context, the present
study aimed to investigate the antineoplastic potential of plant tinctures obtained from species collected in the Reserva Natural Vale (Linhares, Espírito Santo, Brazil) against PGCCs/MNGCs generated in vitro from the MCF-7 breast cancer cell line, integrating
phytochemical, bioinformatic, and cellular approaches. Tinctures of Virola gardneri and Geissospermum laeve were prepared and characterized by gas chromatography–mass spectrometry (GC–MS), enabling the identification of bioactive metabolites with
potential pharmacological activity. The identified compounds were subsequently used for molecular target prediction and protein–protein interaction network (PPIN) construction, revealing hub proteins and biological pathways mainly associated with
inflammation, stress response, cell proliferation, angiogenesis, extracellular matrix remodeling, and cell cycle regulation. In parallel, a chemical hypoxia model using cobalt chloride (CoCl2 ) was successfully established to induce PGCC/MNGC
formation in MCF-7 cells, which exhibited a significant increase in nuclear area and morphological alterations consistent with polyploidization. Cell viability assays (MTT) demonstrated concentration-dependent responses for both tinctures, allowing the
selection of the experimental concentration employed in subsequent analyses. Morphometric evaluation by immunofluorescence combined with digital image analysis demonstrated that treatment with Geissospermum laeve tincture significantly reduced
the frequency of CoCl2 -induced PGCCs/MNGCs, as well as the mean nuclear area of these cells, indicating a modulatory effect on tumor cell plasticity. Collectively, the experimental and in silico findings suggest that the metabolites identified in the
investigated plant species target molecular pathways involved in tumor adaptation to stress and reinforce the pharmacological potential of native flora as a source of bioactive compounds for the development of complementary therapeutic strategies
against breast cancer.

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