Nuclear estrogen receptor targeted photodynamic therapy: Selective uptake and killing of MCF-7 breast cancer cells by a C17α-alkynylestradiol-porphyrin conjugate
✍ Scribed by Narasimha Swamy; Ajay Purohit; Ana Fernandez-Gacio; Graham B. Jones; Rahul Ray
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 404 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
We hypothesized that over‐expression of estrogen receptor (ER) in hormone‐sensitive breast cancer could be harnessed synergistically with the tumor‐migrating effect of porphyrins to selectively deliver estrogen‐porphyrin conjugates into breast tumor cells, and preferentially kill the tumor cells upon exposure to red light. In the present work we synthesized four (4) conjugates of C~17~‐α‐alkynylestradiol and chlorin e6‐dimethyl ester with varying tether lengths, and showed that all these conjugates specifically bound to recombinant ERα. In a cellular uptake assay with ER‐positive MCF‐7 and ER‐negative MDA‐MB 231 human breast cancer cell‐lines, we observed that one such conjugate (E~17~‐POR, XIV) was selectively taken up in a dose‐dependent and saturable manner by MCF‐7 cells, but not by MDA‐MB 231 cells. Furthermore, MCF‐7 cells, but not MDA‐MB 231 cells, were selectively and efficiently killed by exposure to red light after incubation with E~17~‐POR. Therefore, the combination approach, including drug‐ and process modalities has the potential to be applied clinically for hormone‐sensitive cancers in organs where ER is significantly expressed. This could potentially be carried out either as monotherapy involving a photo‐induced selective destruction of tumor cells and/or adjuvant therapy in post‐surgical treatment for the destruction of residual cancer cells in tissues surrounding the tumor. J. Cell. Biochem. 99: 966–977, 2006. © 2006 Wiley‐Liss, Inc.