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

Abstract

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 IC50 values. Honokiol was chosen as the leading compound, and its IC50 ranged from 12 to 20 μM, whereas for other tested lignans, the IC50 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.

Natural Compound Honokiol and Its Application against Fulvestrant-Resistant Breast Cancer Cells: An In Vitro Challenge

“…We have chosen a number of lignans (arctiin, honokiol, matairesinol, pinoresinol, myrislignan, enterodiol, and enterolactone) based on their published anticancer activity toward different types of neoplasms [6,10]. Earlier, we studied the effects of lignans on hydroxytamoxifenresistant cells MCF7/HT and showed that honokiol exhibited a significant antiproliferative effect [11].…”

Combination of metformin and gallic acid induces autophagy and apoptosis in human breast cancer cells

“…Combination therapy is a new and effective strategy in cancer treatment. Several studies show that using metformin in combination with other chemotherapy or non-chemotherapy medications can positively affect the prevention and treatment of breast cancer ( 18 19 20 ).…”