[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), an organometallic derivative of the irreversible cyclooxygenase-1/2 (COX-1/2) inhibitor acetylsalicylic acid (ASS), demonstrated high growth-inhibitory potential against various tumor cell lines and inhibition of both COX isoenzymes. With the objective of increasing the selectivity for COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 of the ASS moiety, respectively. Increased COX-2 selectivity is desirable as this isoenzyme is predominantly related to the development of cancer and abnormal tissue growth. The new compounds were investigated in comprehensive cellular biological assays to identify the impact of the chlorine substitution at the complex on COX-1/2 inhibition, antiproliferative activity, apoptosis, metabolic activity, cell-based COX inhibition, and cellular uptake. Chlorination distinctly reduced the effects at isolated COX-1 (about 25% inhibition at 10 μM; Co-ASS: 82.7%), while those at COX-2 remained almost unchanged (about 65% inhibition at 10 μM; Co-ASS: 78.5%). In cellular systems, with exception of the 6-Cl derivative, all compounds showed notable antitumor activity in COX-1/2 expressing tumor cells (HT-29 (IC = 1.5-2.7 μM), MDA-MB-231 (IC = 5.2-8.0 μM)), but were distinctly less active in the COX-1/2-negative MCF-7 breast cancer cell line (IC = 15.2-22.9 μM). All complexes possess high selectivity for tumor cells, because they did not influence the growth of the non-tumorigenic, human bone marrow stromal cell line HS-5. These findings clearly demonstrate that the interference with the COX-1/2 cascade contributes to the mode of anticancer action of the cobalt alkyne complexes.
The habit of cushion growth positively affects plant temperature but at the same may increase the risk of occasional overheating. In order to determine the adaptive response to short‐term heat stress, we exposed S. acaulis cushions at field sites to controlled heat treatments using infrared lamps. Natural diurnal changes in heat tolerance were monitored at alpine sites and at a site distinctly below the natural distribution boundary, where higher temperatures were expected. The range of heat tolerance limits in summer, 45.5 ‐ 54.5 °C (9 K), exceeded that reported for other alpine species (0.1 ‐ 5 K) and even that for total seasonal changes (5 ‐ 8 K). Heat tolerance either increased or decreased on most days (80 %). The maximum diurnal increase was + 4.7 K. Under the experimental conditions heat hardening started at leaf temperatures around 30 °C and proceeded at mean rates of 1.0 ± 0.5 K/h. The onset of functional disturbances in photosystem II also occurred at 30 °C. Heating rates exceeding those naturally found above 30 °C (> 10 K/h) appeared to retard heat hardening. During summer average leaf temperature maxima were 12.4 K (600 m) and 13.0 K (1945 m) higher than air temperature which corroborates the heat trapping nature of cushion plants. At 600 m, as compared to 1945 m, cushions experienced significantly higher leaf temperature maxima (+ 8.8 K) and exceeded 30 °C on most days (80 %). This resulted in a significantly higher heat tolerance (LT50) at 600 m (51.7 ± 0.2 °C) than at 1945 m (49.8 ± 0.2 °C). The fast short‐term changes of heat tolerance in summer help S. acaulis to cope with the occasional diurnal short‐term heat stress associated with cushion growth.
The significance of leaf rosette closure for survival of drought and heat under high irradiation on alpine rock sites was investigated in the cushion forming rosette plant, Saxifraga paniculata Mill. With decreasing water content the leaves fold over the rosette centre reducing reversibly the evaporative leaf surface area by 80%. Internal water redistribution driven by an osmotic gradient from older to younger leaves occurs. The oldest leaves dry out to promote the survival of the individual. Leaf temperatures above 45 °C (which match heat tolerance limits 45–57 °C; LT50) co‐occurred with low substrate water potentials (less than – 0·5 MPa) on 11·3% of summer days. Shading by leaves can be crucial to surviving high temperatures as it keeps the rosette centre up to 10 °C colder. Mutual shading prevented sustained drought‐induced photoinhibition in upper leaf surfaces at relative water contents below 60%. In exposed lower leaf surfaces restoration of photosystem II took several days. Leaf temperatures above 40 °C (21·3% of summer days) induced photoinhibition in situ. Periods with sufficient water supply can be fully utilized as rehydration is fast (< 12 h) and exposes the upper leaf surfaces that showed only minor photoinhibition. By reversible leaf rosette closure environmental extremes that otherwise could exceed tolerance are efficiently avoided.
The response of effective quantum yield of photosystem 2 (∆F/F m ') to temperature was investigated under field conditions (1 950 m a.s.l.) in three alpine plant species with contrasting leaf temperature climates. The in situ temperature response did not follow an optimum curve but under saturating irradiances [PPFD >800 µmol(photon) m -2 s -1 ] highest ∆F/F m ' occurred at leaf temperatures below 10 °C. This was comparable to the temperature response of antarctic vascular plants. Leaf temperatures between 0 and 15 °C were the most frequently (41 to 56 %) experienced by the investigated species. At these temperatures, ∆F/F m ' was highest in all species (data from all irradiation classes included) but the species differed in the temperature at which ∆F/F m ' dropped below 50 % (Soldanella pusilla >20 °C, Loiseleuria procumbens >25 °C, and Saxifraga paniculata >40 °C). The in situ response of ∆F/F m ' showed significantly higher ∆F/F m ' values at saturating PPFD for the species growing in full sunlight (S. paniculata and L. procumbens) than for S. pusilla growing under more moderate PPFD. The effect of increasing PPFD on ∆F/F m ', for a given leaf temperature, was most pronounced in S. pusilla. Despite the broad diurnal leaf temperature amplitude of alpine environments, only in S. paniculata did saturating PPFD occur over a broad range of leaf temperatures (43 K). In the other two species it was half of that (around 20 K). This indicates that the setting of environmental scenarios (leaf temperature×PPFD) in laboratory experiments often likely exceeds the actual environmental demand in the field.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.