Cancer cells uptake porphyrinsviaheme carrier protein 1

Abstract

Although exogenous porphyrin accumulation in cancer cells is important for the success of photodynamic therapies, the mechanism is not clear. We hypothesized that a newly reported transporter, heme carrier protein 1 (HCP1), is highly expressed in cancer cells, and transports porphyrins into the cells. We investigated the following three unknowns: whether cancer cells take up hematoporphyrin derivative via HCP1, whether HCP1 is involved in photodynamic therapies, and whether cancer cells highly express HCP1. First, when HCP1-overexpressed cells were treated with hematoporphyrin derivative and then exposed to an eximer laser beam, they emitted a significantly higher intensity of hematoporphyrin derivative fluorescence and became more susceptible to the laser beam than control. Second, when three other types of cancer cells with silenced HCP1 were treated with hematoporphyrin derivative and then exposed to the laser beam, they emitted a significantly lower intensity of hematoporphyrin derivative fluorescence. Third, non-cancer cells slightly expressed HCP1; on the other hand, the three other types of cancer cells clearly expressed HCP1. These results indicated that cancer cells uptake hematoporphyrin derivative via HCP1 and over-expression of HCP1 increases the efficacy of photodynamic therapies by increasing porphyrin accumulation in the cells. This is the first report about a transporter of porphyrin in cancer cells.