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1.
Front Plant Sci ; 9: 1936, 2018.
Article in English | MEDLINE | ID: mdl-30687345

ABSTRACT

It has long been known that hormones affect the interaction of a phytopathogen with its host plant. The pathogen can cause changes in plant hormone homeostasis directly by affecting biosynthesis or metabolism in the plant or by synthesizing and secreting the hormone itself. We previously demonstrated that pathogenic fungi of the Fusarium species complex are able to produce three major types of hormones: auxins, cytokinins, and gibberellins. In this work, we explore changes in the levels of these hormones in maize and mango plant tissues infected with Fusarium. The ability to produce individual phytohormones varies significantly across Fusarium species and such differences likely impact host specificity inducing the unique responses noted in planta during infection. For example, the production of gibberellins by F. fujikuroi leads to elongated rice stalks and the suppression of gibberellin biosynthesis in plant tissue. Although all Fusarium species are able to synthesize auxin, sometimes by multiple pathways, the ratio of its free form and conjugates in infected tissue is affected more than the total amount produced. The recently characterized unique pathway for cytokinin de novo synthesis in Fusarium appears silenced or non-functional in all studied species during plant infection. Despite this, a large increase in cytokinin levels was detected in F. mangiferae infected plants, caused likely by the up-regulation of plant genes responsible for their biosynthesis. Thus, the accumulation of active cytokinins may contribute to mango malformation of the reproductive organs upon infection of mango trees. Together, our findings provide insight into the complex role fungal and plant derived hormones play in the fungal-plant interactions.

2.
Food Chem Toxicol ; 50(11): 4068-76, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22939933

ABSTRACT

Brassinosteroids (BRs) are a group of polyhydroxylated sterol derivatives with important regulatory roles in various plant physiological processes. The aim of this study was to examine the mechanism of the antiproliferative activity of natural BRs 28-homocastasterone (28-homoCS) and 24-epibrassinolide (24-epiBL) in hormone-sensitive and -insensitive (LNCaP and DU-145, respectively) human prostate cancer cell lines. The effects of BRs on prostate cancer cells were surveyed using flow cytometry, Western blotting, TUNEL, DNA ladder assays and immunofluorescence analyses. The studied BRs inhibited cell growth and induced G(1) blocks in LNCaP cells accompanied by reductions in cyclin D(1), CDK4/6 and pRb expression. Following BR treatment of DU-145 cells, increases in proportions of cells in the G(2)/M phase of cell cycle were observed, accompanied by down-regulation of cyclins A and B(1). Changes in AR localization patterns in LNCaP cells treated with BRs were shown by immunofluorescence analysis. Furthermore, apoptotic detection methods demonstrated induction of apoptosis mediated by BRs in both cell lines, although changes in the expression of apoptosis-related proteins were modulated differently by 28-homoCS and 24-piBL in each cell line. The studied BRs seem to exert potent growth inhibitory and pro-apoptotic effects and could be therefore highly valuable new candidates for prostate anticancer drugs.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Brassinosteroids/pharmacology , Prostatic Neoplasms/drug therapy , Cell Cycle/drug effects , Cell Line, Tumor , Cholestanones/pharmacology , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/metabolism , Drug Screening Assays, Antitumor , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Steroids, Heterocyclic/pharmacology
3.
J Med Chem ; 54(9): 3298-305, 2011 May 12.
Article in English | MEDLINE | ID: mdl-21438635

ABSTRACT

Analogues of the potent cytotoxic saponin OSW-1 were prepared from the readily available steroidal 16ß,17α,22-triol. The new 22-deoxo-23-oxa analogues of OSW-1 were screened against eight cancer cell lines and normal human fibroblasts. The analogues proved to be slightly less active than OSW-1 but also less toxic to normal cells. They induce concentration- and time-dependent apoptosis of mammalian cancer cells with caspase-3 activation.


Subject(s)
Antineoplastic Agents/chemical synthesis , Cholestenones/chemical synthesis , Saponins/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis , Caspase 3/metabolism , Caspase 7/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cholestenones/chemistry , Cholestenones/pharmacology , Drug Screening Assays, Antitumor , Enzyme Activation , Fibroblasts/drug effects , Humans , Saponins/chemistry , Saponins/pharmacology , Stereoisomerism , Structure-Activity Relationship
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