Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin.

Autor: Mikhaevich EI; Department of Experimental Tumour Biology, Blokhin N.N. National Medical Research Centre of Oncology, the Ministry of Health of the Russian Federation, Moscow, Russia., Sorokin DV; Department of Experimental Tumour Biology, Blokhin N.N. National Medical Research Centre of Oncology, the Ministry of Health of the Russian Federation, Moscow, Russia., Scherbakov AM; Department of Experimental Tumour Biology, Blokhin N.N. National Medical Research Centre of Oncology, the Ministry of Health of the Russian Federation, Moscow, Russia.
Jazyk: angličtina
Zdroj: Research in pharmaceutical sciences [Res Pharm Sci] 2023 Aug 20; Vol. 18 (5), pp. 580-591. Date of Electronic Publication: 2023 Aug 20 (Print Publication: 2023).
DOI: 10.4103/1735-5362.383712
Abstrakt: Background and Purpose: Primary and metastatic breast cancers still represent an unmet clinical need for improved chemotherapy and hormone therapy. Considerable attention has been paid to natural anticancer compounds, especially lignans. The study aimed to evaluate the activity of several lignans against breast cancer cells and assess the effect of leading lignans on signaling pathways in combination with metformin.
Experimental Approach: Human breast cancer cell lines MCF7 (hormone-dependent), MDA-MB-231, and SKBR3 (hormone-independent) were used. A hormone-resistant MCF7/hydroxytamoxifen (HT) subline was obtained by long-term cultivation of the MCF7 line with hydroxytamoxifen. Antiproliferative activity was assessed by the MTT test; the expression of signaling pathway proteins was evaluated by immunoblotting analysis.
Findings/results: We evaluated the antiproliferative activity of lignans in breast cancer cells with different levels of hormone dependence and determined the relevant IC 50 values. Honokiol was chosen as the leading compound, and its IC 50 ranged from 12 to 20 μM, whereas for other tested lignans, the IC 50 exceeded 50 μM. The accumulation of cleaved PARP and a decrease in the expression of Bcl-2 and ERα in MCF7/HT were induced following the combination of honokiol with metformin.
Conclusions and Implications: Honokiol demonstrated significant antiproliferative activity against both hormone-dependent breast cancer cells and lines with primary and acquired hormone resistance. The combination of honokiol with metformin is considered an effective approach to induce death in hormone-resistant cells. Honokiol is of interest as a natural compound with antiproliferative activity against breast cancers, including resistant tumors.
Competing Interests: The authors declared no conflict of interest in this study.
(Copyright: © 2023 Research in Pharmaceutical Sciences.)
Databáze: MEDLINE
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