Cantharidin and norcantharidin inhibit caprine luteal cell steroidogenesis in vitro

Twu, Nae‐Fang; Srinivasan, Ramanujam; Chou, Chung‐Hsi; Wu, Leang‐Shin; Chiu, Chien Chao

doi:10.1016/j.etp.2010.06.003

Cited by 10 publications

(7 citation statements)

References 28 publications

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“…Incubation with pregnenolone markedly increases progesterone production by MA-10 cells [33]. We found that cotreatment with IA did not alter the effect of pregnenolone on progesterone production, indicating that IA does not regulate 3 β -HSD activity (Figures 5(c) and 5(d)).…”

Section: Discussionmentioning

confidence: 82%

“…To evaluate the role of P450scc in IA actions, we used a substrate of P450scc (22R-OHC), which freely crosses the aqueous space between the outer and inner mitochondrial membranes [34]. After confirming that incubation with 22R-OHC boosts progesterone production in MA-10 cells [33], we cotreated cells with IA and found that progesterone production was not decreased by IA treatment (Figures 5(a) and 3(b)). Since IA did not alter 3 β -HSD activity, the lack of effect of IA on 22R-OHC-stimulated progesterone production shows that IA does not regulate P450scc activity.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Tsui

Wang

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Tsui

Wang

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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“…Li and Casida concluded that the enzyme in which CTD is bonded was phosphoprotein phosphatases 1 (PP1) and 2A (PP2A, AC type, EC 3.1.3.16). The special attention is that they might influence secretory processes, phosphatase‐linked mechanisms that have been implicated extensively in several endocrine tissues, including islets of langerhans and chromaffin and pituitary cells . PP1 and PP2A exert also their effects by modulating the activity of cyclin‐dependent kinases (cdk) and the retinoblastoma protein (pRb), and knowing that the activation of cdk/cyclin complexes requires the phosphorylation of a conserved threonine residue, as well as the removal of inhibitory phosphorylations, these enzymes play a crucial role in other biological process .…”

Section: The Phospho Protein Phosphatases: Pp1 and Pp2a The Main Biomentioning

confidence: 99%

Cantharidin‐Based Small Molecules as Potential Therapeutic Agents

2013

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Chemical and pharmacological information on cantharidin-based small molecules was analyzed. The review summarizes new facts about blister beetles' metabolites for the period 2006-2012. General synthetic approaches to cantharidin-based small molecules as well as their chemical transformations and biological activities related to cantharidin, norcantharidin, cantharidimide, and norcantharimide analogs, especially their inhibitory activity of phosphoprotein phosphatases in cancer treatment, were discussed in this mini review, which could help to design new small molecule modulators for other biological models.Key words: anticancer activity, blister beetles, cantharidin analogs, Diels-Alder cycloaddition reactions, drug design and development, protein phosphatases inhibitory activity With the development in the natural product chemistry, giving many interesting objects to study from the structural, synthetic, and pharmacological standpoints, the organic synthesis had evolved at the same rate with the generation of molecules/molecular assemblies with welldefined biological functions, and within this challenging task in the biology-oriented synthesis field, the design and development of more efficient chemical reactions and methodologies would revolutionize the next generation of chemical and biological research. Secondary metabolites of plants and animals are the main objects to study phytochemistry and organic chemistry, as shown by their centennial history that has successfully promoted the discovery and drug development. According to a recent analysis, in the last 25 years, nearly half of the drugs currently in clinical use belong to drugs of natural origin (1,2). Therefore, the success of drug discovery based on nature's secondary metabolites depends on how these natural substances are considered, mainly by medicinal and organic chemists, as source of inspiration rather than target molecules (3-6).For centuries, it has well known that many plants (shrubs, trees and grasses) possess a wide spectrum of medicinal properties and that bacterium and fungi are also capable of generating toxic constituents that inhibit the growth of other organisms in their proximity. These kingdoms have provided us more information, regarding the biological interactions of small molecules (SMs), to understand and encourage our investigations in the discovery and development of new SMs with marked physiological activities (7,8). In addition, these SMs are also useful for investigating biological systems as effective tools to elucidate the mechanism of important cellular processes that are based purely on (i) the performance of enzymatic reactions and (ii) protein-protein interactions, where the bioactive SMs are called bioprobes, and more importantly, (iii) the fact that they allow the rapid and conditional modulation of biological functions often in a reversible, dose-dependent manner (9,10).In contrast to plants and bacteria, the invertebrate animal kingdom, to which belong different insects (about a million species) including beetles,...

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“…Though CTD has a variety of therapeutic uses, it has a number of toxic side effects, such as kidney and gastrointestinal damage and disruption of reproductive functions107, 117, 118. Its closely related naturally occurring analogue, norcantharidin (NCTD), has similar therapeutic uses but with lower toxicity risk117, 118.…”

Section: Coleoptera (Beetles)mentioning

confidence: 99%

“…Its closely related naturally occurring analogue, norcantharidin (NCTD), has similar therapeutic uses but with lower toxicity risk117, 118. As a chemo-preventive agent NCTD has inhibited tumor progression in non-small cell lung cancer (NSCLC), prostate cancer and leukemia, in vitro , through cell-cycle arrest and apoptosis119, 120, 121.…”

Section: Coleoptera (Beetles)mentioning

confidence: 99%

Insects: an underrepresented resource for the discovery of biologically active natural products

Seabrooks¹,

Hu²

2017

Acta Pharmaceutica Sinica B

112

123

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Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

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Cantharidin and norcantharidin inhibit caprine luteal cell steroidogenesis in vitro

Cited by 10 publications

References 28 publications

Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Cantharidin‐Based Small Molecules as Potential Therapeutic Agents

Insects: an underrepresented resource for the discovery of biologically active natural products

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