Penitrem A – Chemotherapy & Insecticide Use

 

 

This page lists medical journal articles discussing the use of penitrem A for chemotherapy or as an insecticide.

The Health Effects of Penitrem A page of the Paradigm Change site provides further information on the effects of this mycotoxin.

 

Chemotherapy

Goda AA, Siddique AB, Mohyeldin M, Ayoub NM, El Sayed KA. The Maxi-K (BK) Channel Antagonist Penitrem A as a Novel Breast Cancer-Targeted Therapeutic. Mar Drugs. 2018 May 11;16(5). PMID: 29751615

Penitrem A is a selective BK channel antagonist with reported antiproliferative and anti-invasive activities against multiple malignancies, including breast cancer. Collectively, the BK channel antagonists represented by penitrem A can be novel sensitizing, chemotherapeutics synergizing, and therapeutic agents for targeted BC therapy.

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Sallam AA, Ayoub NM, Foudah AI, Gissendanner CR, Meyer SA, El Sayed KA. Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells. Eur J Med Chem. 2013;70:594-606. PMID: 24211635

The study herein reports the novel ability of penitrem A to suppress total β-catenin levels in MDA-MB-231 mammary cancer cells. Nine new penitrem analogs (10-18) were semisynthetically prepared, in an attempt to identify pharmacophores correlated with BK channel inhibition and tremorgenicity of penitrems and decrease their toxicity. Although new analogs were generally less active than parent compound 1, some showed no BK channel inhibition or tremorgenicity and retained the ability of penitrem A (1) to suppress total β-catenin levels in MDA-MB-231 cells. Paspaline (6) and emindole SB (7), both lacking BK channel inhibition and tremorgenicity, represent the simplest indole diterpene skeleton that retains the antiproliferative, antimigratory and total β-catenin suppressing effects shown by the more complex penitrem A (1).

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Sallam AA, Houssen WE, Gissendanner CR, Orabi KY, Foudah AI, El Sayed KA. Bioguided discovery and pharmacophore modeling of the mycotoxic indole diterpene alkaloids penitrems as breast cancer proliferation, migration, and invasion inhibitors. Medchemcomm. 2013 Oct;4(10). PMID: 24273638

Bioassay-guided fractionation afforded the indole diterpene alkaloids penitrems A, B, D, E and F as well as paspaline and emnidole SB. These compounds showed good antiproliferative, antimigratory and anti-invasive properties against human breast cancer cells.

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Abdullaev Iskandar F., Rudkouskaya Alena, Mongin Alexander A., Kuo Yu-Hung H.. Calcium-activated potassium channels BK and IK1 are functionally expressed in human gliomas but do not regulate cell proliferation. PloS one. 2010;5. PMID: 20808839 

Gliomas are morbid brain tumors that are extremely resistant to available chemotherapy and radiology treatments. In this work we characterized the expression and functional contribution to proliferation of Ca(2+)-activated K(+) channels in human glioblastoma cells. Inhibitors of BK (paxilline and penitrem A) and IK1 channels (clotrimazole and TRAM-34) reduced U251 and U87 proliferation in an additive fashion, while the selective blocker of SK channels UCL1848 had no effect. However, the antiproliferative properties of BK and IK1 inhibitors were seen at concentrations that were higher than those necessary to inhibit channel activity.

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Gessner G., Schönherr K., Soom M., et al. BKCa channels activating at resting potential without calcium in LNCaP prostate cancer cells. The Journal of membrane biology. 2005;208:229–240. PMID: 16604468 

Large-conductance Ca2+-dependent K+ (BK(Ca)) channels are activated by intracellular Ca2+ and membrane depolarization in an allosteric manner. We investigated the pharmacological and biophysical characteristics of a BK(Ca)-type K+ channel in androgen-dependent LNCaP(lymph node carcinoma of the prostatecells with novel functional properties, here termed BK(L). K+ selectivity, high conductance, activation by Mg2+ or NS1619, and inhibition by paxilline and penitrem A largely resembled the properties of recombinant BK(Ca) channels.

Insecticide

Dowd P. F., Cole R. J., Vesonder R. F.. Toxicity of selected tremorgenic mycotoxins and related compounds to Spodoptera frugiperda and Heliothis zea. The Journal of antibiotics. 1988;41:1868–1872. PMID: 3209479

A series of tremorgenic mycotoxins and related compounds were tested for oral toxicity to the fall armyworm (Spodoptera frugiperda) and corn earworm (Heliothis zea) by incorporation of materials into artificial diets and examining mortality and weights after 7 days. Significant mortality to both insect species was caused with dihydroxyaflavinine and roseotoxin B, while significant mortality to H. zea was also caused by penitrem A at 25 ppm.

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González M. Carmen, Lull Cristina, Moya Pilar, Ayala Ildefonso, Primo Jaime, Primo Yúfera Eduardo. Insecticidal activity of penitrems, including penitrem G, a new member of the family isolated from Penicillium crustosum. Journal of agricultural and food chemistry. 2003;51:2156–2160.

 

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