-
1.
Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis.
Virdis, P, Migheli, R, Bordoni, V, Fiorentino, FP, Sanna, L, Marchesi, I, Pintore, G, Galleri, G, Muroni, MR, Bagella, L, et al
International journal of molecular medicine. 2021;(6)
-
-
Free full text
-
Abstract
Multiple myeloma (MM) is an aggressive B cell malignancy. Substantial progress has been made in the therapeutic context for patients with MM, however it still represents an incurable disease due to drug resistance and recurrence. Development of more effective or synergistic therapeutic approaches undoubtedly represents an unmet clinical need. Tomentosin is a bioactive natural sesquiterpene lactone extracted by various plants with therapeutic properties, including anti‑neoplastic effects. In the present study, the potential antitumor activity of tomentosin was evaluated on the human RPMI‑8226 cell line, treated with increasing tomentosin concentration for cytotoxicity screening. The data suggested that both cell cycle arrest and cell apoptosis could explain the antiproliferative effects of tomentosin and may result in the inhibition of RPMI‑8226 cell viability. To assess differentially expressed genes contributing to tomentosin activity and identify its mechanism of action, a microarray gene expression profile was performed, identifying 126 genes deregulated by tomentosin. To address the systems biology and identify how tomentosin deregulates gene expression in MM from a systems perspective, all deregulated genes were submitted to enrichment and molecular network analysis. The Protein‑Protein Interaction (PPI) network analysis showed that tomentosin in human MM induced the downregulation of genes involved in several pathways known to lead immune‑system processes, such as cytokine‑cytokine receptor interaction, chemokine or NF‑κB signaling pathway, as well as genes involved in pathways playing a central role in cellular neoplastic processes, such as growth, proliferation, migration, invasion and apoptosis. Tomentosin also induced endoplasmic reticulum stress via upregulation of cyclic AMP‑dependent transcription factor ATF‑4 and DNA damage‑inducible transcript 3 protein genes, suggesting that in the presence of tomentosin the protective unfolded protein response signaling may induce cell apoptosis. The functional connections analysis executed using the Connectivity Map tool, suggested that the effects of tomentosin on RPMI‑8226 cells might be similar to those exerted by heat shock proteins inhibitors. Taken together, these data suggested that tomentosin may be a potential drug candidate for the treatment of MM.
-
2.
A novel strigolactone-miR156 module controls stomatal behaviour during drought recovery.
Visentin, I, Pagliarani, C, Deva, E, Caracci, A, Turečková, V, Novák, O, Lovisolo, C, Schubert, A, Cardinale, F
Plant, cell & environment. 2020;(7):1613-1624
Abstract
miR156 is a conserved microRNA whose role and induction mechanisms under stress are poorly known. Strigolactones are phytohormones needed in shoots for drought acclimation. They promote stomatal closure ABA-dependently and independently; however, downstream effectors for the former have not been identified. Linkage between miR156 and strigolactones under stress has not been reported. We compared ABA accumulation and sensitivity as well as performances of wt and miR156-overexpressing (miR156-oe) tomato plants during drought. We also quantified miR156 levels in wt, strigolactone-depleted and strigolactone-treated plants, exposed to drought stress. Under irrigated conditions, miR156 overexpression and strigolactone treatment led to lower stomatal conductance and higher ABA sensitivity. Exogenous strigolactones were sufficient for miR156 accumulation in leaves, while endogenous strigolactones were required for miR156 induction by drought. The "after-effect" of drought, by which stomata do not completely re-open after rewatering, was enhanced by both strigolactones and miR156. The transcript profiles of several miR156 targets were altered in strigolactone-depleted plants. Our results show that strigolactones act as a molecular link between drought and miR156 in tomato, and identify miR156 as a mediator of ABA-dependent effect of strigolactones on the after-effect of drought on stomata. Thus, we provide insights into both strigolactone and miR156 action on stomata.
-
3.
Effects of diet on skin sensitization by nickel, poison ivy, and sesquiterpene lactones.
An, N, Pourzal, S, Luccioli, S, Vukmanović, S
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2020;:111137
Abstract
Skin contact or exposure to sensitizers often occurs as a consequence of occupational exposures (e.g. poison ivy in forestry), wearing jewelry (e.g. nickel), or use of cosmetics (e.g. fragrances). However, many of the known skin sensitizers or their chemical variants are also consumed orally through foods or other sources. Since oral exposure to antigenic substances can lead to tolerance, consumption of sensitizers may impact the development and potency of skin sensitization, especially if the sensitizer is consumed early in life, prior to the first skin contact. To address this issue, we have reviewed human clinical and epidemiological literature relevant to this subject and evaluated whether early oral exposures to relevant sensitizers, or their chemical variants, are associated with reduced prevalence of skin sensitization to three main allergic sensitizers - nickel, urushiols of poison ivy, and sesquiterpene lactones of chrysanthemum and other plants.
-
4.
Exogenous strigolactones impact metabolic profiles and phosphate starvation signalling in roots.
Gamir, J, Torres-Vera, R, Rial, C, Berrio, E, de Souza Campos, PM, Varela, RM, Macías, FA, Pozo, MJ, Flors, V, López-Ráez, JA
Plant, cell & environment. 2020;(7):1655-1668
Abstract
Strigolactones (SLs) are important ex-planta signalling molecules in the rhizosphere, promoting the association with beneficial microorganisms, but also affecting plant interactions with harmful organisms. They are also plant hormones in-planta, acting as modulators of plant responses under nutrient-deficient conditions, mainly phosphate (Pi) starvation. In the present work, we investigate the potential role of SLs as regulators of early Pi starvation signalling in plants. A short-term pulse of the synthetic SL analogue 2'-epi-GR24 promoted SL accumulation and the expression of Pi starvation markers in tomato and wheat under Pi deprivation. 2'-epi-GR24 application also increased SL production and the expression of Pi starvation markers under normal Pi conditions, being its effect dependent on the endogenous SL levels. Remarkably, 2'-epi-GR24 also impacted the root metabolic profile under these conditions, promoting the levels of metabolites associated to plant responses to Pi limitation, thus partially mimicking the pattern observed under Pi deprivation. The results suggest an endogenous role for SLs as Pi starvation signals. In agreement with this idea, SL-deficient plants were less sensitive to this stress. Based on the results, we propose that SLs may act as early modulators of plant responses to P starvation.
-
5.
Synthetic strigolactone (rac-GR24) alleviates the adverse effects of heat stress on seed germination and photosystem II function in lupine seedlings.
Omoarelojie, LO, Kulkarni, MG, Finnie, JF, Pospíšil, T, Strnad, M, Van Staden, J
Plant physiology and biochemistry : PPB. 2020;:965-979
Abstract
There is increasing experimental evidence that strigolactones, a class of carotenoid-derived sesquiterpenoid hormones, and their downstream signal components play a role in plant resilience to abiotic stress. Strigolactones positively influence plant coping mechanisms in response to abiotic stressors like drought and high salinity. In this study, we examined the effects of rac-GR24 (a synthetic strigolactone analog) and strigolactone inhibitors on the physiological and molecular responses associated with thermotolerance during seed germination and seedling development in Lupinus angustifolius under heat stress. Photosystem I & II functions were also evaluated via Chl a fluorescence transient analysis in heat stressed lupine seedlings. Our results suggest a putative role for GR24 in mediating tolerance to heat stress during seed germination and seedling development albeit these responses appeared independent of D14-mediated signalling. Seeds primed with GR24 had the highest of all germination indices, enhanced proline content and reduced peroxidation of lipids. GR24 also enhanced the activities of enzymes of the antioxidant and glyoxalase systems in lupine seedlings. The JIP-test indicated that GR24 conferred resistance to heat stress-induced damage to the oxygen evolution complex while also preventing the inactivation of PSII reaction centres thus ensuring PSII thermotolerance.
-
6.
How Do Strigolactones Ameliorate Nutrient Deficiencies in Plants?
Yoneyama, K
Cold Spring Harbor perspectives in biology. 2019;(8)
-
-
Free full text
-
Abstract
Strigolactones (SLs), a group of plant secondary metabolites, play an important role as a host recognition signal for symbiotic arbuscular mycorrhizal (AM) fungi in the rhizosphere. SLs promote symbioses with other beneficial microbes, including root nodule bacteria. Root parasitic weeds also take advantage of SLs as a clue to locate living host roots. In plants, SLs function as plant hormones regulating various growth and developmental processes including shoot and root architectures. Plants under nutrient deficiencies, especially that of phosphate, promote SL production and exudation to attract symbionts and to optimize shoot and root architecture.
-
7.
Strigolactone-nitric oxide interplay in plants: The story has just begun.
Kolbert, Z
Physiologia plantarum. 2019;(3):487-497
Abstract
Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during plant development and stress responses. This review aims to discuss the so far available data regarding SLs-NO interplay in plant systems. The majority of the few articles dealing with SL-NO interplay focuses on the root system and it seems that NO can be an upstream negative regulator of SL biosynthesis or an upstream positive regulator of SL signaling depending on the nutrient supply. From the so far published results it is clear that NO modifies the activity of target proteins involved in SL biosynthesis or signaling which may be a physiologically relevant interaction. Therefore, in silico analysis of NO-dependent posttranslational modifications in SL-related proteins was performed using computational prediction tools and putative NO-target proteins were specified. The picture is presumably more complicated, since also SL is able to modify NO levels. As a confirmation, author detected NO levels in different organs of max1-1 and max2-1 Arabidopsis and compared to the wild-type these mutants showed enhanced NO levels in their root tips indicating the negative effect of endogenous SLs on NO metabolism. Exogenous SL analogue-triggered NO production seems to contradict the results of the genetic study, which is an inconsistency should be taken into consideration in the future. In the coming years, the link between SL and NO signaling in further physiological processes should be examined and the possibilities of NO-dependent posttranslational modifications of SL biosynthetic and signaling proteins should be looked more closely.
-
8.
Alleviation of drought stress in grapevine by foliar-applied strigolactones.
Min, Z, Li, R, Chen, L, Zhang, Y, Li, Z, Liu, M, Ju, Y, Fang, Y
Plant physiology and biochemistry : PPB. 2019;:99-110
Abstract
Drought is one of the major abiotic stress factors that affect grape growth and yield, which in turn negatively affects the grape and wine production industry. Developing effective approaches to improve grapevine tolerance to drought stress is a priority for viticulture. Strigolactones, a newly discovered class of carotenoid-derived phytohormones, have been found to participate in various physiological processes. Herein, the effect of strigolactones (SLs) on grape seedlings under drought stress was investigated. Two-year-old grape seedlings (Vitis vinifera L.) were sprayed with 3 doses of rac-GR24 (1 μM, 3 μM and 5 μM), a synthesized strigolactone, and then were subjected to 7% (w/v) polyethylene glycol (PEG-6000) to simulate the drought conditions. Synthetic GR24 treated plants showed higher tolerance to drought stress with regard to lower electrolyte leakage, stomatal opening, reactive oxygen species (ROS), and higher relative water content, chlorophyll content, photosynthesis rate and malondialdehyde (MDA) content. GR24 application also decreased the levels of indoleacetic acid (IAA) and zeatin riboside (ZR), while increasing the level of abscisic acid (ABA), both in the roots and leaves under drought stress. These results suggested that foliar application of GR24 could ameliorate the adverse effects of drought due to its regulation of stomatal closure through ABA or ROS, and modulation of chlorophyll components and photosynthesis, as well as activation of the antioxidant defense capacity. Cross-talk with other hormones, especially ABA, was also suggested to be one of the important mechanism during this process. This study contributes to our current understanding of GR24-induced drought tolerance in grapevines.
-
9.
Antiproliferative Effects of Cynaropicrin on Anaplastic Thyroid Cancer Cells.
Lepore, SM, Maggisano, V, Lombardo, GE, Maiuolo, J, Mollace, V, Bulotta, S, Russo, D, Celano, M
Endocrine, metabolic & immune disorders drug targets. 2019;(1):59-66
Abstract
BACKGROUND The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects. OBJECTIVE Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action. METHOD MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation. RESULTS Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production. CONCLUSION These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.
-
10.
Strigolactones: mediators of osmotic stress responses with a potential for agrochemical manipulation of crop resilience.
Cardinale, F, Korwin Krukowski, P, Schubert, A, Visentin, I
Journal of experimental botany. 2018;(9):2291-2303
-
-
Free full text
-
Abstract
After quickly touching upon general aspects of strigolactone biology and functions, including structure, synthesis, and perception, this review focuses on the role and regulation of the strigolactone pathway during osmotic stress, in light of the most recent research developments. We discuss available data on organ-specific dynamics of strigolactone synthesis and interaction with abscisic acid in the acclimatization response, with emphasis on the ecophysiological implications of the effects on the stomatal closure process. We highlight the importance of considering roots and shoots separately as well as combined versus individual stress treatments; and of performing reciprocal grafting experiments to work out organ contributions and long-distance signalling events and components under more realistic conditions. Finally, we elaborate on the question of if and how synthetic or natural strigolactones, alone or in combination with crop management strategies such as grafting, hold potential to maximize crop resilience to abiotic stresses.