Photosystem II (PSII) is a large homodimeric protein-cofactor complex that acts as light-driven water:plastoquinone oxidoreductase and is located in the photosynthetic thylakoid membrane of plants, green algae and cyanobacteria. The principal function of PSII is to oxidize two water molecules at the unique Mn 4 Ca cluster to molecular (atmospheric) oxygen, 4 protons and 4 electrons. The protons serve to drive ATP synthetase and the electrons reduce plastoquinone (Q B ) to plastoquinol (Q B H 2 ) that is exported and delivers the electrons (through the cytochrome b 6 f complex) to photosystem I. Here the electrons gain a high reducing potential and serve at NADP reductase to generate NADPH that together with ATP reduces CO 2 to carbohydrates in the Calvin cycle. The crystal structure of PSII from Thermosynechococcus elongatus at 2.9-Å resolution [1] allowed the unambiguous assignment of all 20 protein subunits and complete modeling of all 35 chlorophyll a, 2 pheophytin, 2 cytochrome, 2 plastoquinone, and 12 carotenoid molecules, 25 integral lipids, 1 chloride ion and the Mn 4 Ca cluster per PSII monomer. The presence of a third plastoquinone Q C and a second plastoquinone-transfer channel, which were not observed before, suggest mechanisms for plastoquinolplastoquinone exchange, and we calculated other possible water or dioxygen and proton channels. Putative oxygen positions obtained from Xenon derivative crystals indicate a role for lipids in oxygen diffusion to the cytoplasmic side of PSII. The chloride position suggests a role in protontransfer reactions because it is bound through a putative water molecule to the Mn 4 Ca cluster at a distance of 6.5 Å and is close to two possible proton transfer channels.

Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the β-catenin signaling pathway in the presence or absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell migration, invasion, sphere-forming, and β-catenin signaling pathway were explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone, miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere-forming potential in HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the β-catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the β-catenin pathway via miR-200c.

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These observations indicate that miR-222 and miR-155 could induce radiation resistance in colorectal cancer by targeting PTEN and FOXO3a genes, respectively. Therefore, miR-222 and miR-155 can be suggested as good biomarkers of CRC radiation response.