Frontiers in pharmacology · 2026
Selective biological activity of parthenolide derivatives - stizolin, stizolicin, and izospiciformin - isolated from the leaves of Stizolophus balsamita, in different breast cancer molecular subtypes in vitro.
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Nawrot Joanna, Totoń Ewa, Dziechciowska Iga, Boruta Agnieszka, Gołębiowska Małgorzata, Idzik Małgorzata, Kaczmarek Mariusz, Rubiś Błażej, Gornowicz-Porowska Justyna, Lisiak Natalia
Аннотация
INTRODUCTION: Breast cancer is the most frequently diagnosed malignant tumor and one of the leading causes of cancer deaths. Combination therapies, chemotherapy, and hormone therapy have indeed revolutionized the treatment of breast cancer, but they have not eliminated the occurrence of side effects. Among different anticancer strategies, plant-derived compounds appear to play a critical role in both prevention and therapy. They have been utilized in folk medicine for years, revealing anti-inflammatory, antimigraine, and anticancer properties. In particular, parthenolide derivatives have been shown to act as adjuvant agents in the treatment of various malignancies. Especially when provided with modifications that increase their bioavailability and stability.
METHODS: Here, we present the cell type-selective biological activity of parthenolide derivatives-stizolin, stizolicin, and izospiciformin-isolated from the leaves of Stizolophus balsamita, in a panel of three different molecular subtypes of breast cancer cell (MCF7, MDA-MB-231, and SK-BR-3). Viability, clonogenic potential, apoptosis, and autophagy processes have been verified to explain the biological activity of the studied natural compounds.
RESULTS: The highest biological activity was demonstrated by the stizolin (with the IC50 from 1.3 to 4.3 μg/mL depending on cell line), which exhibited antiproliferative, proapoptotic, and proautophagic properties in the studied breast cancer cells, particularly in the HER2-positive breast cancer cell line (SK-BR-3), demonstrated by PARP1/2 cleavage, Bax/Bcl2 status increase, and confirmed by LC3II/LC3I, mTOR, and p62 proteins alterations.
CONCLUSION: Our results indicate that the studied compounds exhibit compound-dependent biological activity, and selectivity across different molecular subtypes of breast cancer.
METHODS: Here, we present the cell type-selective biological activity of parthenolide derivatives-stizolin, stizolicin, and izospiciformin-isolated from the leaves of Stizolophus balsamita, in a panel of three different molecular subtypes of breast cancer cell (MCF7, MDA-MB-231, and SK-BR-3). Viability, clonogenic potential, apoptosis, and autophagy processes have been verified to explain the biological activity of the studied natural compounds.
RESULTS: The highest biological activity was demonstrated by the stizolin (with the IC50 from 1.3 to 4.3 μg/mL depending on cell line), which exhibited antiproliferative, proapoptotic, and proautophagic properties in the studied breast cancer cells, particularly in the HER2-positive breast cancer cell line (SK-BR-3), demonstrated by PARP1/2 cleavage, Bax/Bcl2 status increase, and confirmed by LC3II/LC3I, mTOR, and p62 proteins alterations.
CONCLUSION: Our results indicate that the studied compounds exhibit compound-dependent biological activity, and selectivity across different molecular subtypes of breast cancer.