G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric regions and in the promoter and untranslated regions (UTR) of cancer-related genes, such as RAS and MYC. Extensive research has suggested that G4 is a potential molecular target for cancer therapy. Here, we reviewed G4 ligands as photosensitizers for cancer photodynamic therapy (PDT), which is a minimally invasive therapeutic approach. The photosensitizers, such as porphyrins, were found to be highly toxic against cancer cells via the generation of reactive oxidative species (ROS) upon photo-irradiation. Several porphyrin derivatives and analogs, such as phthalocyanines, which can generate ROS upon photo-irradiation, have been reported to act as G4 ligands. Therefore, they have been implicated as promising photosensitizers that can selectively break down cancer-related DNA and RNA forming G4. In this review, we majorly focused on the potential application of G4 ligands as photosensitizers, which would provide a novel strategy for PDT, especially molecularly targeted PDT (mtPDT).

Structural selectivity of G-quadruplex ligands is essential for cellular applications since there is an excess of nucleic acids forming duplex structures in living cells. In this study, we developed new...

Cancer cells generally exhibit increased iron uptake, which contributes to their abnormal growth and metastatic ability. Iron chelators have thus recently attracted attention as potential anticancer agents. Here, we show that deferriferrichrysin (Dfcy), a natural product from Aspergillus oryzae acts as an iron chelator to induce paraptosis (a programmed cell death pathway characterized by ER dilation) in MCF‐7 human breast cancer cells and H1299 human lung cancer cells. We first examined the anticancer efficacy of Dfcy in cancer cells and found that Dfcy induced ER dilation and reduced the number of viable cells. Extracellular signal‐related kinase (ERK) was activated by Dfcy treatment, and the MEK inhibitor U0126, a small molecule commonly used to inhibit ERK activity, prevented the increase in ER dilation in Dfcy‐treated cells. Concomitantly, the decrease in the number of viable cells upon treatment with Dfcy was attenuated by U0126. Taken together, these results demonstrate that the iron chelator Dfcy exhibits anticancer effects via induction of ERK‐dependent paraptosis.

We identified cytosine-rich regions adjacent to guanine-rich regions in the TMPRSS2 gene, which showed structural competition between a G-quadruplex and a hairpin loop. Furthermore, this competition significantly affected transcription efficiency.

Tumor suppressor p53 plays a central role in the DNA damage response. DNA-damaging agents modulate nuclear actin dynamics, influencing cell behaviors; however, it remains unclear whether p53 affects the structure of nuclear actin filaments. Here, we show that actin filament formation in the nucleus induced by the DNA-damaging agent doxorubicin (DOXO) treatment is suppressed by p53 via caspase-1 expression. In DOXO-treated cells, the nuclear actin filament formation was promoted by p53 depletion. Whilst the DOXO treatment caused an increase in caspase-1 expression, which was largely attenuated by p53 depletion, overexpression of caspase-1 reduced DOXO-induced formation of nuclear actin filaments in p53-depleted cells. By contrast, caspase-1 inhibition, together with DOXO treatment, induced nuclear actin filament formation even in cells bearing wild-type p53. These results suggest that p53-mediated expression of caspase-1 suppresses nuclear actin filament formation. In addition, we found that expression of nLifeact-GFP, which contains the filamentous actin (F-actin)-binding peptide and nuclear localization signal (NLS), promoted the bundling of nuclear actin filaments and strongly altered the chromatin structure in DOXO-treated, p53-depleted cells. Given that the loss of p53 is associated with cancer progression, the results of this study raised the possibility that artificial reinforcement of nuclear actin filaments by nLifeact-GFP may enhance the cytotoxicity effect of DNA-damaging agents in aggressive cancer cells.