4-hydroxytamoxifen is an active metabolite of the drug Tamoxifen. Tamoxifen is the first endocrine therapy drug and one of the most prescribed to treat breast cancer since more than four decades. The therapeutic indication of Tamoxifen is the treatment of hormone-dependent breast cancers expressing estrogen receptor α (ERα), the target of Tamoxifen.

‍

To assess the selectivity of 4-hydroxytamoxifen, we designed a 6-tissue co-culture system consisting of encapsulated ERα- breast cancer spheroids (HCC1395, red; MDA-MB-231, purple; SK-BR3, orange) and encapsulated ERα+ breast cancer spheroids (MCF-7, green; T47D, uncolored; BT-474, blue), treated with 4-hydroxytamoxifen 5 µM for 48 h (Figure 1). A staining with LIVE/DEAD dyes was performed to measure the cytotoxicity induced by 4-hydroxytamoxifen. The colors of the capsules were used to independently and simultaneously measure the cytotoxic activity of 4-hydroxytamoxifen in the six tissue types of the co-culture (Figure 2).

High reliability of the identification of the different types of spheroids based on their respective capsule color and homogeneous encapsulated spheroid counts (Figure 3).

Much higher sensitivity of ERα+ spheroids compared to ERα- spheroids (Figure 3).

V Craig Jordan. Tamoxifen: a most unlikely pioneering medicine. Nature Reviews Drug Discovery, 2: 205-213 (2003).

Dai X, Cheng H, Bai Z, Li J. Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping. Journal of Cancer, 8(16): 3131-3141 (2017).