β-lapachone impairs viability, migration, and epithelial-mesenchymal transition in mammary tumor spheroids

Breast cancer is the main cancer among women globally and the second most prevalent in Brazil. In the 2023-2025 triennium, it was estimated that nearly 20,000 deaths occurred. The poor prognosis is mainly associated with the occurrence of metastasis. New therapeutic strategies are needed to control the tumor progression and/or improve cancer patients' quality of life. β-lapachone (β-lap) is a natural naphthoquinone obtained from the inner bark of the lapacho trees, native to South America. This compound has several pharmacological properties, including antitumor effects in various solid tumors. Three-dimensional (3D) culture models better replicate the interactions between cells and cells with the extracellular matrix, mimicking tumor structure and behavior. They exhibit in vitro drug responses more similar to in vivo conditions. Given the limited research investigating the anticancer potential of β-lap using 3D cultures, this study aimed to evaluate its effects in breast tumor spheroids.

MCF-7 spheroids were produced through our scaffold-free 3D system. Thereafter, we investigated the cytotoxic and antimetastatic properties of β-lap by analyzing spheroid diameter, cell death, viability, and proteins related to the epithelial-mesenchymal transition (EMT) process (E-cadherin and vimentin).

β-lap reduced spheroid diameter and induced cell death at 1.2 mg/L after 72 h. The compound decreased viability in a dose-dependent manner: 25% at 1.2 mg/L (after 48 h), 35-45% at 2.5 mg/L, and up to 50% at 5 and 10 mg/L. It further progressively inhibited cell migration and modulated EMT, increasing E-cadherin expression by 18.4% and reducing vimentin by 34.3%.

The natural compound β-lap has the potential to be a promising anticancer agent for breast cancer.