Natural photosensitizers in photodynamic therapy: In vitro activity against monolayers and spheroids of human colorectal adenocarcinoma SW480 cells.

Photodynamic Therapy (PDT), is a treatment option for cancer.It involves the photochemical interaction of light, photosensitizer (PS) and molecular oxygen to produce radical species as well as singlet oxygen which induce cell death. Anthraquinones (AQs) have been extensively studied with respect to their UV/Vis absorption characteristics and their photosensitizing properties in photodynamic reactions. We study the photoactivity of different natural AQs (Parietin, Soranjidiol and Rubiadin) in treating monolayers and multicellular tumor spheroids (MCTSs). Rubiadin and soranjidiol were isolated and purified from the stem and leaves of Heterophyllae pustulata, and PTN was from the liquen Teloschistes flavicans by using repeated combination of several chromatographic techniques. Monolayer and spheroids of human colorectal adenocarcinoma SW480 cells were incubated with different concentrations of the AQs and then irradiated at room temperature. 24 h post-PDT cell viability, nuclear morphology and type of cell death were analyzed. We observed that Soranjidiol and Rubiadin showed no significant difference in the photosensitizing ability on monoculture of colon cancer cells (LD80 at 50 µM and 10 J/cm2, for both AQs). Nevertheless, for Parietin (PTN) LD80 was achieved at (20 µM using the same light dose (10 J/cm2). The death mechanism induced post-PDT was necrosis by use of Soranjidol and Rubiadin and apoptosis by use of PTN. Furthermore, in MCTSs of 300 and 900 µm, the treatment PTN- PDT produces the greatest cytotoxic effect. The three AQs analyzed could be promising chemotherapeutic candidates as anticancer PDT agents.

Contribution of resident and recruited macrophages to the photodynamic intervention of colorectal tumor microenvironment.

The study of cellular interactions in the tumor microenvironment has become one of the main areas of research in the fight against cancer. Tumor-associated macrophages (TAMs) influence tumor progression and therapy response due to its functional plasticity. Regarding cancer treatment, photodynamic therapy (PDT) is a minimally invasive and clinically approved procedure that involves the administration of a photosensitizer (PS), a nontoxic photosensitizing drug which is selectively retained in neoplastic tissue. Here, we investigated the role of resident and nonresident macrophages in the context of a PDT-treated colorectal tumor by developing a combination of 2-D and three-dimensional (3-D) experimental platform, recreating tumor-stroma interactions in vitro. Enhancement of cytotoxicity of PDT was achieved in the presence of nonresident macrophages which had a strong anti-tumor phenotype mediated by the production of nitric oxide, IL-6, and tumor necrosis factor alpha (TNF-α). On the contrary, tumor resident macrophages induced a pro-tumor phenotype promoting tumor cell migration and endothelial stimulation. Due to their plasticity, tumor-resident or tumor-recruited macrophages can differentially influence the response of tumors to PDT, so their multifactorial roles should be considered in the overall design of anti-tumor therapeutic.

Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment.

Photodynamic therapy (PDT) is a novel cancer treatment. It involves the activation of a photosensitizer (PS) with light of specific wavelength, which interacts with molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) that lead to tumor cell death. When a tumor is treated with PDT, in addition to affect cancer cells, the extracellular matrix and the other cellular components of the microenvironment are altered and finally this had effects on the tumor cells survival. Furthermore, the heterogeneity in the availability of nutrients and oxygen in the different regions of a tridimensional tumor has a strong impact on the sensitivity of cells to PDT. In this review, we summarize how PDT affects indirectly to the tumor cells, by the alterations on the extracellular matrix, the cell adhesion and the effects over the immune response. Also, we describe direct PDT effects on cancer cells, considering the intratumoral role that autophagy mediated by hypoxia-inducible factor 1 (HIF-1) has on the efficiency of the treatment.