title: The pro-apoptotic and anti-invasive effects of hypericin-mediated photodynamic therapy are enhanced by hyperforin or aristoforin in HT-29 colon adenocarcinoma cells.
abstract: Photodynamic therapy is a rapidly-developing anti-cancer approach for the treatment of various types of malignant as well as non-malignant diseases. In this study, hypericin-mediated photodynamic therapy (HY-PDT) in sub-optimal dose was combined with hyperforin (HP) or its stable derivative aristoforin (AR) in an effort to improve efficacy on the cellular level. The logic of this combination is based on the fact that both bioactive compounds naturally occur in plants of Hypericum sp. At relatively low concentrations up to 5 μM, hyperforin and aristoforin were able to stimulate onset of apoptosis in HT-29 colon adenocarcinoma cells exposed to HY-PDT, inhibit cell cycle progression, suppress expression of matrixmetalloproteinases-2/-9 together with cell adhesivity, thereby affecting the clonogenic potential of the cells. As the action of aristoforin was more pronounced, in line with our assumption, these changes were also linked in this case with hypericin accumulation and increased ROS generation leading to dissipation of mitochondrial membrane potential in a significant portion of the cells, as well as activation of caspase-3. Comparison of HT-29 cells to another colon adenocarcinoma-derived cell line HCT-116 demonstrated significant differences in sensitivity of different cell lines to PDT, however, accumulated effect of HY-PDT with HP/AR proved similar in both tested cell lines. The presented data may help to elucidate the mechanisms of action for different bioactive constituents of St. John's wort, which are increasingly recognized as being able to regulate a variety of pathobiological processes, thus possessing potential therapeutic properties.
authors.affiliation: Institute of Biology and Ecology, Faculty of Sciences, P.J. Šafárik University in Košice, Moyzesova 11, 040 01 Košice, Slovakia.
authors.forename: Martina
authors.initials: M
authors.lastname: Šemeláková
authors.forename: Jaromír
authors.initials: J
authors.lastname: Mikeš
authors.forename: Rastislav
authors.initials: R
authors.lastname: Jendželovský
authors.forename: Peter
authors.initials: P
authors.lastname: Fedoročko
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D019073:HT29 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D009361:Neoplasm Invasiveness; D010569:Perylene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; C502222:Aristoforin; D017382:Reactive Oxygen Species; D013729:Terpenes; D010569:Perylene; C004965:hypericin; D010696:Phloroglucinol; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C001654:hyperforin