Background: p53 function is lost in more than 50% of tumors.Results: p53 aggregates into amyloid oligomers and fibrils in vitro and in breast cancer tissues; mutant p53 seeds amyloid aggregation of WT p53, a behavior typical of a prion.Conclusion: Prion-like aggregation is crucial for the negative dominance of mutant p53.Significance: The inhibition of aggregation could be a target for cancer therapy.

Gap junction channels, formed by connexins (Cx), are involved in the maintenance of tissue homeostasis, cell growth, differentiation, and development. Several studies have shown that Cx43 is involved in the control of wound healing in dermal tissue. However, it remains unknown whether Cx43 plays a role in the control of liver fibrogenesis. Our study investigated the roles of Cx43 heterologous deletion on carbon tetrachloride (CCl(4))-induced hepatic fibrosis in mice. We administered CCl(4) to both Cx43-deficient (Cx43(+/-)) and wild-type mice and examined hepatocellular injury and collagen deposition by histological and ultrastructural analyses. Serum biochemical analysis was performed to quantify liver injury. Hepatocyte proliferation was analyzed immunohistochemically. Protein and messenger RNA (mRNA) expression of liver connexins were evaluated using immunohistochemistry as well as immunoblotting analysis and quantitative real-time PCR. We demonstrated that Cx43(+/-) mice developed excessive liver fibrosis compared with wild-type mice after CCl(4) -induced chronic hepatic injury, with thick and irregular collagen fibers. Histopathological evaluation showed that Cx43(+/-) mice present less necroinflammatory lesions in liver parenchyma and consequent reduction of serum aminotransferase activity. Hepatocyte cell proliferation was reduced in Cx43(+/-) mice. There was no difference in Cx32 and Cx26 protein or mRNA expression in fibrotic mice. Protein expression of Cx43 increased in CCl(4)-treated mice, although with aberrant protein location on cytoplasm of perisinusoidal cells. Our results demonstrate that Cx43 plays an important role in the control and regulation of hepatic fibrogenesis.

It is estimated that more than 600,000 new cases of cancer will be reported in Brazil during the 2018–2019 biennium, especially with regard to prostate, breast, lung and colorectal cancers. Due to the high prevalence, incidence and mortality rates of these diseases, cancer campaigns such as ‘Pink October’ and ‘Blue November’ were strongly promoted in the past decade throughout the country to raise awareness of breast and prostate cancer, respectively. Nevertheless, whether the implementation of these campaigns has been proven efficient is still unknown. In the present study, we analysed the effectiveness of these campaigns on eliciting population online interest for cancer information. The Google Trends database was evaluated for the relative Internet search popularity for the terms ‘breast cancer’ and ‘prostate cancer’ from 2014 to 2019. Aside from some regional differences, we found that there was a high demand for ‘breast cancer’ and, to a lesser extent, ‘prostate cancer’ searches in a seasonal fashion (during October and November, respectively). Despite the worldwide high incidence of lung and colorectal cancers, searches including these keywords did not show increases in any specific period of the year, demonstrating the efficiency of the ‘Pink October’ and ‘Blue November’ campaigns in engaging the interest of the Brazilian population on the subject. These results allow us to infer that campaigns are effective in mobilising the attention of the Brazilian population with regard to breast and prostate cancers, but the practical aspects in reducing incidence and mortality should still be discussed.

Resveratrol is a promising chemopreventive agent that mediates many cellular targets involved in cancer signaling pathways. p53 has been suggested to play a role in the anticancer properties of resveratrol. We investigated resveratrol-induced cytotoxicity in H1299 cells, which are non-small lung cancer cells that have a partial deletion of the gene that encodes the p53 protein. The results for H1299 cells were compared with those for three cell lines that constitutively express wild-type p53: breast cancer MCF-7, adenocarcinomic alveolar basal epithelia A549 and non-small lung cancer H460. Cell viability assays revealed that resveratrol reduced the viability of all four of these cell lines in a dose- and time-dependent manner. MCF-7, A549 and H460 cells were more sensitive to resveratrol than were H1299 cells when exposed to the drug for 24 h at concentrations above 100 µM. Resveratrol also increased the p53 protein levels in MCF-7 cells without altering the p53 mRNA levels, suggesting a post-translational modulation of the protein. The resveratrol-induced cytotoxicity in these cells was partially mediated by p53 and involved the activation of caspases 9 and 7 and the cleavage of PARP. In H1299 cells, resveratrol-induced cytotoxicity was less pronounced and (in contrast to MCF-7 cells) cell death was not accompanied by caspase activation. These findings are consistent with the observation that MCF-7 cells were positively labeled by TUNEL following exposure to 100 µM resveratrol whereas H1299 cells under similar conditions were not labeled by TUNEL. The transient transfection of a wild-type p53-GFP gene caused H1299 cells to become more responsive to the pro-apoptotic properties of resveratrol, similarly to findings in the p53-positive MCF-7 cells. Our results suggest a possible therapeutic strategy based on the use of resveratrol for the treatment of tumors that are typically unresponsive to conventional therapies because of the loss of normal p53 function.