Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined.

Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells. Here we report for the first time that SLs induce DNA damage in the form of DNA double-strand breaks (DSBs) and activate the DNA damage response signaling by inducing phosphorylation of ATM, ATR and DNA-PKcs and co-localization of the DNA damage signaling protein, 53BP1, with γH2AX nuclear foci. We further report that in addition to DSBs induction, SLs simultaneously impair DSBs repair, mostly homology-directed repair (HDR) and to a lesser extent non-homologous end joining (NHEJ). In response to SLs, RAD51, the homologous DSB repair protein, is ubiquitinated and targeted for proteasomal degradation and it fails to co-localize with γH2AX foci. Interestingly, SLs synergize with DNA damaging agents-based therapeutics. The combination of PARP inhibitors and SLs showed an especially potent synergy, but only in BRCA1-proficient cells. No synergy was observed between SLs and PARP inhibitors in BRCA1-deficient cells, supporting a role for SLs in HDR impairment. Together, our data suggest that SLs increase genome instability and cell death by a unique mechanism of inducing DNA damage and inhibiting DNA repair.

The optimisation study of the fabrication of a compact TiO2 blocking layer (via Spray Pyrolysis\ud Deposition) for poly(3-hexylthiopene) (P3HT) for Solid State Dye Sensitized Solar Cells\ud (SDSCs) is reported. We used a novel spray TiO2 precursor solution composition obtained\ud by adding acetylacetone to a conventional formulation (Diisopropoxytitanium bis(acetylacetonate)\ud in ethanol). By Scanning Electron Microscopy a TiO2 layer with compact morphology\ud and thickness of around 100 nmis shown. Through a Tafel plot analysis an enhancement of the\ud device diode-like behaviour induced by the acetylacetone blocking layer respect to the conventional\ud one is observed. Significantly, the device fabricatedwith the acetylacetone blocking\ud layer shows an overall increment of the cell performance with respect to the cellwith the conventional\ud one (DJsc/Jsc = +13.8%, DFF/FF = +39.7%, DPCE/PCE = +55.6%). A conversion efficiency\ud optimumis found for 15 successive spray cycles where the diode-like behaviour of the acetylacetone\ud blocking layer is more effective. Over three batches of cells (fabricated with P3HT and\ud dye D35) an average conversion efficiency value of 3.9% (under a class A sun simulator with 1\ud sun A.M. 1.5 illumination conditions) was measured. From the best cell we fabricated a conversion\ud efficiency value of 4.5% was extracted. This represents a significant increment with\ud respect to previously reported values for P3HT/dye D35 based SDSCs

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This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total 6 synthesis in sustaining their pharmacological development as an alternative to isolation. This paper also outlines the 7 feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may 8 become a real future perspective. This review demonstrates that total chemical synthesis is a fruitful means of yielding 9 fungal derivatives as aided by recent technological and innovative advancements.