Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress

T-LAK-originated protein kinase (TOPK) overexpression is a feature of multiple cancers, yet is absent from most phenotypically normal tissues. As such, TOPK expression profiling and the development of TOPK-targeting pharmaceutical agents have raised hopes for its future potential in the development of targeted therapeutics. Results presented in this paper confirm the value of TOPK as a potential target for the treatment of solid tumours, and demonstrate the efficacy of a TOPK inhibitor (OTS964) when used in combination with radiation treatment. Using H460 and Calu-6 lung cancer xenograft models, we show that pharmaceutical inhibition of TOPK potentiates the efficacy of fractionated irradiation. Furthermore, we provide in vitro evidence that TOPK plays a hitherto unknown role during S phase, showing that TOPK depletion increases fork stalling and collapse under conditions of replication stress and exogenous DNA damage. Transient knockdown of TOPK was shown to impair recovery from fork stalling and to increase the formation of replication-associated single-stranded DNA foci in H460 lung cancer cells. We also show that TOPK interacts directly with CHK1 and Cdc25c, two key players in the checkpoint signalling pathway activated after replication fork collapse. This study thus provides novel insights into the mechanism by which TOPK activity supports the survival of cancer cells, facilitating checkpoint signalling in response to replication stress and DNA damage.Subject terms: Tumour biomarkers, Oncogenes, Preclinical research     

Impact of melatonin and tryptophan on water stress tolerance in white lupine (Lupinus termis L.)

Melatonin  has been identified as a signal molecule that regulates plant responses to different abiotic and biotic stresses. Melatonin (MT) and its precursor tryptophan (Try) have a major role in improving plant stress tolerance to different environmental stresses such as water deficiency. The rapid increase in the Egyptian population caused insufficient protein sources, especially those of animal origin, in their diet. The possible solution is to augment the diet with legumes such as white lupine which are relatively rich in protein. Thus, the current experimental work was carried out to find changes in growth, biochemical aspects and yield quantity and quality of white lupine plant with spraying of both MT and Try at different concentrations on plant shoot under water deficit stress conditions. Results showed that water deficit (75 or 50% of water irrigation requirements; WIR) caused significant reduction in growth, photosynthetic pigments, indole acetic acid and yield compared with those received 100% WIR. Seed yield significantly decreased (p < 0.05) by 26.98 and 41.64% by decreasing WIR to 75 and 50%. The decrease was accompanied by significant increase in phenolic contents, hydrogen peroxide, lipid peroxidation and some antioxidant enzymes, while nitrate reductase enzyme was decreased. However, external application of either MT or Try significantly alleviated the adverse effects of water deficit (growth suppression), since MT or Try-treated plants recovered more quickly than untreated plants. Moreover, MT or Try—treated plants had higher photosynthetic pigments, indole acetic acid, phenolic, as well as yield quantity and quality under the three WIR as compared with untreated plants. Melatonin treatment at 100 µM and Tryptophan at 200 µM increased weight of seeds/plant by 78.29 and 52.19%, 71.49 and 43.78% and 41.21 and 13.07% in plants irrigated with 100, 75 and 50% WIR, respectively. Exogenous MT and Try significantly reduced hydrogen peroxide and malondialdehyde content, while markedly increased the activities of antioxidant enzymes and nitrate reductase under different WIR. Finally, the current study concluded that MT and Try treatments alleviated the detrimental effects of water deficiency and accelerated the recovery mainly via improving white lupine plants tolerance in forms of enhancing photosynthetic pigments, indole acetic acid, phenolic and antioxidant capacity.     

Studies of human malignant lymphomas after treatment with endoxan. I. Cytochemical studies in the respiratory enzymes succinic dehydrogenase and cytochrome oxidase.

The respiratory enzymes succinic dehydrogenase and cytochrome oxidase were studied in normal lymph node and malignant lymphoma cells under the effect of endoxan treatment. It is concluded that the decrease in the respiratory enzymes in lymphoma cells may be taken as one of the outstanding differences between the neoplastic and normal tissues.     

Evaluation of growth and nutritional value of Brassica microgreens grown under red,blue and green LEDs combinations

Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization, nutritional composition profile of 21 varieties representing five species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%); red:blue 80:20 and 20:80 (R₈₀:B₂₀ and R₂₀:B₈₀), or red:green:blue 70:10:20 and 20:10:70 (R₇₀:G₁₀:B₂₀ and R₂₀:G₁₀:B₇₀). Results indicated that supplemental lighting with green LEDs (R₇₀:G₁₀:B₂₀) enhanced vegetative growth and morphology, while blue LEDs (R₂₀:B₈₀) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R₇₀:G₁₀:B₂₀). Remarkably, under the green LEDs combination (R₇₀:G₁₀:B₂₀) conditions, the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content.