Tumor promoting constituent ofEuphorbia serrata L. latex

Upadhyay, Rajiv R.; Ansarin, Morteza; Zarintan, M. H.; Shakui, P.

doi:10.1007/bf01927623

Cited by 11 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fli-1 transactivating compounds are structurally related to diterpenes, a family of drugs including 12-O-tetradecanoylphorbol-13-acetate (TPA), which promotes tumorigenesis when applied to the skin [25, 26]. To determine their biological activity, leukemic cell lines expressing high or low levels of Fli-1 were treated with the compounds.…”

Section: Resultsmentioning

confidence: 99%

A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis

et al. 2016

View full text Add to dashboard Cite

The ETS-related transcription factor Fli-1 affects many developmental programs including erythroid and megakaryocytic differentiation, and is frequently de-regulated in cancer. Fli-1 was initially isolated following retrovirus insertional mutagenesis screens for leukemic initiator genes, and accordingly, inhibition of this transcription factor can suppress leukemia through induction of erythroid differentiation. To search for modulators of Fli-1, we hereby performed repurposing drug screens with compounds isolated from Chinese medicinal plants. We identified agents that can transcriptionally activate or inhibit a Fli-1 reporter. Remarkably, agents that increased Fli-1 transcriptional activity conferred a strong anti-cancer activity upon Fli-1-expressing leukemic cells in culture. As opposed to drugs that suppress Fli1 activity and lead to erythroid differentiation, growth suppression by these new Fli-1 transactivating compounds involved erythroid to megakaryocytic conversion (EMC). The identified compounds are structurally related to diterpene family of small molecules, which are known agonists of protein kinase C (PKC). In accordance, these PKC agonists (PKCAs) induced PKC phosphorylation leading to activation of the mitogen-activated protein kinase (MAPK) pathway, increased cell attachment and EMC, whereas pharmacological inhibition of PKC or MAPK diminished the effect of our PKCAs. Moreover, in a mouse model of leukemia initiated by Fli-1 activation, the PKCA compounds exhibited strong anti-cancer activity, which was accompanied by increased presence of CD41/CD61 positive megakaryocytic cells in leukemic spleens. Thus, PKC agonists offer a novel approach to combat Fli-1-induced leukemia, and possibly other cancers,by inducing EMC in part through over-activation of the PKC-MAPK-Fli-1 pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Biological investigations revealed that euphorbia factor L 5 (93) and compounds 139 and 140 are tumor promoters. 100,101 2.3.6 Other activities. Kansuiphorin A (94) showed antiviral activity and it is suggested that this compound prevents viral pneumonia in mice.…”

Section: Tiglianes †mentioning

confidence: 99%

Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators

et al. 2014

View full text Add to dashboard Cite

Covering: 1973 to 2013. The biological activities of tigliane, lathyrane, ingenane, casbane, jatropholane and premyrsinane diterpenoids which contain the gem-dimethylcyclopropyl unit are described. Particular attention is given to their anti-viral, anti-microbial and cytotoxic activities. In the main text there are 132 references. The electronic supplementary information contains tables listing 424 of these diterpenoids, their occurrence and biological activity together with the references.

show abstract

“…238 In 1971, Adolf and Hecker showed that the carcinogenic activity in mice due to oil extracted from the seeds of E. lathyris L. resulted from the irritating activity of the esters of ingenol 7-hydroxy-lathyrol and a monoester of ingenol. 240 Previously, Upadhyay et al (1976) evaluated the latex extracted from E. serrata, from which ingenol-3-palmitate originated, which exhibited irritant and carcinogenic activities in an ear and dorsal skin test of NMRI mice. 241 Opferkuch and Hecker (1982) isolated compounds from E. ingens E. Mey.…”

Section: Ingenane/diterpenes Toxicities and Tumor Promotion Effectsmentioning

confidence: 99%

The Role of Ingenane Diterpenes in Cancer Therapy: From Bioactive Secondary Compounds to Small Molecules

Silva

Faleiros

Silva

et al. 2022

Natural Product Communications

View full text Add to dashboard Cite

Diterpenes are a class of critical taxonomic markers of the Euphorbiaceae family, representing small compounds (eg, molecules) with a wide range of biological activities and multi-target therapeutic potential. Diterpenes can exert different activities, including antitumor and multi-drug resistance-reversing activities, and antiviral, immunomodulatory, and anti-inflammatory effects, mainly due to their great structural diversity. In particular, one polycyclic skeleton has been highlighted: ingenane. Besides this natural diterpene, promising polycyclic skeletons may be submitted to chemical modification—by in silico approaches, chemical reactions, or biotransformation—putatively providing more active analogs (eg, ingenol derivatives), which are currently under pre-clinical investigation. This review outlines the current mechanisms of action and potential therapeutic implications of ingenol diterpenes as small cancer molecules.

show abstract

Tumor promoting constituent ofEuphorbia serrata L. latex

Abstract: Euphorbia serrata latex has initially ingenol-3-palmitate, which by action of silica gel is converted to ingenol-20-palmitate. The former is responsible for the irritant and cocarcinogenic activity of the latex on mouse ear and on mice back skin.

Cited by 11 publications

References 3 publications

A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis

A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis

Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators

The Role of Ingenane Diterpenes in Cancer Therapy: From Bioactive Secondary Compounds to Small Molecules

Contact Info

Product

Resources

About