CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence.

Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2- breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction. The first p21 wave is caused by osmotic stress, leading to p38- and size-dependent accumulation of p21. CDK4/6 inhibitor washout results in some cells entering S-phase. Overgrown cells experience replication stress, resulting in a second p21 wave that promotes cell cycle withdrawal from G2 or the subsequent G1. We propose that the levels of p21 integrate signals from overgrowth-triggered stresses to determine cell fate. This model explains how hypertrophy can drive senescence and why CDK4/6 inhibitors have long-lasting effects in patients.

Enhancing antioxidant systems by preharvest treatments with methyl jasmonate and salicylic acid leads to maintain lemon quality during cold storage.

The effects of preharvest treatments with 0.1 mM methyl jasmonate (MeJA) and 0.5 mM salicylic acid (SA) on quality parameters of lemon fruit and their relationship with antioxidant systems, gene expression and bioactive compounds at harvest and during cold storage were evaluated. Results showed that total antioxidant activity, total phenolic content and the major individual phenolics (hesperidin and eriocitrin) were always higher in treated fruit than in controls. The activity of the antioxidant enzymes catalase, peroxidase and ascorbate peroxidase was also increased at harvest by SA and MeJA treatments, especially the last enzyme, for which the expression of its codifying gene was also enhanced. In addition, treated fruit had lower weight and firmness losses, respiration rate and production of ethylene than controls. Moreover, sugars and organic acids were maintained at higher concentration in flavedo and juice as a consequence of preharvest SA and MeJA treatments, showing an effect on maintaining fruit quality properties.

Pre-harvest methyl jasmonate treatments increase antioxidant systems in lemon fruit without affecting yield or other fruit quality parameters.

BACKGROUND: Jasmonic acid (JA) and its volatile derivative methyl jasmonate (MeJA) are hormones involved in the regulation of many processes in plants and act (when applied as a post- or pre-harvest treatment) to increase fruit bioactive compounds with antioxidant potential. However, there is no literature available regarding the effect of pre-harvest MeJA treatment on lemon fruit antioxidant systems, which was the aim of the present study. RESULTS: MeJA treatment (0.1, 0.5 and 1.0 mmol L-1 ) increased antioxidant compounds, such as phenolics, in the juice and flavedo of 'Fino' and 'Verna' lemons at harvest, with the most effective concentration being 0.1 mmol L-1 in both cultivars. In addition, catalase (CAT), peroxidase (POD) and ascorbate peroxidase (APX) activities were also increased by MeJA treatment, with the highest increases being also found with 0.1 mmol L-1 . The increases in APX and CAT were maintained from one treatment to another during fruit development on the tree, whereas the increase on POD disappeared after 8-10 days of each treatment. For both antioxidant systems, the highest increases were found in lemon harvested at the commercial ripening stage. By contrast, crop yield, fruit ripening process and quality parameters were generally not affected by MeJA treatment. CONCLUSION: Preharvest MeJA treatment could be a useful tool for increasing antioxidant potential and the health beneficial effects of lemon fruit consumption, given the relationship between these properties and phenolic content. Moreover, the increased concentration of phenolics and the activity of antioxidant enzymes in the flavedo of MeJA treated fruit could increase lemon tolerance to chilling injury and decay during postharvest storage. © 2019 Society of Chemical Industry.

Maturity stage at harvest determines the fruit quality and antioxidant potential after storage of sweet cherry cultivars.

Eleven sweet cherry cultivars were harvested at three maturity stages (S1 to S3) based on skin color and stored at 2 degrees C for 16 days and a further period of 2 days at 20 degrees C (shelf life, SL) to analyze quality (color, total soluble solids, and total acidity) and bioactive compounds (total phenolics and anthocyanins) and their relationship to total antioxidant activity (TAA), determined in hydrophilic (H-TAA) or lipophilic (L-TAA) fraction. For all cultivars and maturity stages, the ripening process advanced during postharvest storage with increases in color intensity and decreases in acidity, as well as enhancements in phenolics, anthocyanins, and TAA in both H-TAA and L-TAA, although important differences existed among cultivars. The results showed that sweet cherry should be harvested at stage S3 (4 days later than the commercial harvest date) since after 16 days of cold storage + SL, the highest antioxidant capacity was achieved for both H-TAA and L-TAA.