eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

Abstract

Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M−1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

“…Western blot was performed as described before [19,31]. Briefly, cell lysates of sorted F4/80 + or CD115 …”

“…qRT-PCR was performed as described before [31]. Briefly, RNA in sorted F4/80 + or CD115 + cells was extracted using TRIzol.…”

Enhancing Type I Photochemistry in Photodynamic Therapy Under Near Infrared Light by Using Antennae–Fullerene Complexes

“…Currently, PDT is only used for cancers in very shallow tissues because of the limited ability of red light to penetrate tissues (<5–10 mm) . NIR light (700–1,100 nm) with an approximate penetration depth of 20–30 mm has been reported to be ideal for treating deep‐seated tumors .…”

“…Photodynamic therapy (PDT), a form of light‐based medical treatment, has been developed as salvage or palliative treatment for a wide range of tumors, such as gastrointestinal, breast, skin, and head and neck tumors . PDT has attracted considerable attention because it is minimally invasive and has low mutagenic potential and low systemic toxicity .…”

“…PDT has attracted considerable attention because it is minimally invasive and has low mutagenic potential and low systemic toxicity . In clinical settings, PDT agents (photosensitizers [PSs]) are administered intravenously and target some proteins such as eEF1A1, followed by light irradiation at the tumor sites . PDT has three main components: a PS, oxygen, and light .…”