Hydroxycyperaquinone is a novel sub micromolar

2022-07-25

Hydroxycyperaquinone is a novel sub-micromolar inhibitor of the 20S catalytic core of the 20S proteasome, causing cell death via IRE1α-independent/PERK-dependent pathways. Despite this benzoquinone Phytomedicine 63 (2019) 153017
displayed toxicity against normal cell lines, it Taxol is an important source to develop a new drug inspired in their chemical structure in order to be more selective to cancer cells.
Conflict of interest
Nothing to declare.
Acknowledgments
Supplementary materials
References
Bradford, M.M., 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254.
da Silva, D.C., Andrade, P.B., Valentão, P., Pereira, D.M., 2017. Neurotoxicity of the steroidal alkaloids tomatine and tomatidine is RIP1 kinase- and caspase-independent and involves the eIF2α branch of the endoplasmic reticulum. J. Steroid Biochem. Mol. Biol. 9. r> Kinupp, V.F., 2008. Plantas alimentícias não-convencionais da região metropolitana de porto alegre, RS. RBA 3.
Moreira, M.M., 1990. Benzoquinonas existentes em espécies de Cyperus da flora
Portuguesa - contribuição para o seu conhecimento. Farmacognosia - Faculdade def
Farmácia. Universidade do Porto, pp. 152.
Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells. BMC Complement. Altern. Med. 13, 1472–6882. Peerzada, A.M., Ali, H.H., Naeem, M., Latif, M., Bukhari, A.H., Tanveer, A., 2015. Cyperus rotundus L.: traditional uses, phytochemistry, and pharmacological activities. J. Ethnopharmacol. 174, 540–560.
Pereira, D., Valentão, P., Andrade, P.B., 2018. Tuning protein folding in lysosomal storage diseases: the chemistry behind pharmacological chaperones. Chem. Sci. 9, 1740–1752. Pereira, D.M., Correia-da-Silva, G., Valentão, P., Teixeira, N., Andrade, P.B., 2014a. Anti-Inflammatory effect of unsaturated fatty acids and ergosta-7,22-dien-3-ol from Marthasterias glacialis: prevention of CHOP-mediated ER-stress and NF-κB activation. PLoS One 9, e88341.
Pereira, D.M., Correia-da-Silva, G., Valentão, P., Teixeira, N., Andrade, P.B, 2014b. GC–MS lipidomic profiling of the echinoderm Marthasterias glacialis and screening for activity against human cancer and non-cancer cell lines. Comb. Chem. High Throughput Screen 17, 450–457.
Contents lists available at ScienceDirect
South African Journal of Botany
Berberis hispanica alkaloids extract induced cell death and apoptosis in human laryngeal cancer cells Hep-2
a Laboratoire de Physiologie des Organismes, Equipe de Physiopathologie cellulaire et moléculaire, Faculté des Sciences biologiques, Université des Sciences et Technologies, Houari Boumedienne, (USTHB), BP 32 El Alia, 16011 Alger, Algeria
b Laboratoire Central de Police Scientifique, Département de Sécurité Alimentaire et Environnement, 1 rue Abdelaziz Khelalfa, Châteauneuf, Ben Aknoun, Alger, Algeria
c Laboratoire de botanique médicale, Département de Pharmacie, Université d'Alger, 18 avenue Pasteur, 16100, Alger, Algeria
Article history:
Received in revised form 20 March 2019 Accepted 15 April 2019 Available online xxxx
Edited by JJ Nair
Keywords:
Berberis hispanica alkaloids extract
Cancer cells
Cell cycle
Reactive oxygen species apoptosis
Berberis (Barberry) species contain an important amount of alkaloids and are commonly used in traditional med-icine. Alkaloids are preponderantly characterized by their numerous properties including anticancer activity. The aims of the present study were to investigate the effect and the mechanism of action of the Algerian Berberis hispanica alkaloids extract (BHAE) on Hep-2 laryngeal cancer cells. In this purpose, total alkaloids were extracted from the roots bark of the plant, then, were submitted to HPLC analysis. In order to determine the cells inhibition concentration (IC50), we used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells were enumerated using Trypan blue exclusion assay and viability by cell cycle analysis. The morphology was assessed by coloration with May Grunwald Giemsa (MGG). The evaluation of such stress markers as malondialdehyde (MDA), cytochrome c, p38MAPK, NF-kB, Akt, Erk 1/ 2 and p53 was assessed by colorimetric as-says and western blotting. Our results demonstrated that BHAE contains Berberine, an isoquinoline plant alkaloid. The IC50 was determined at 75 μg/mL and the treatment of Hep-2 cells with this dose showed anti-proliferative effect and increased SubG0 cell population (cells undergoing apoptosis) in treated cells (15.4%). Further, the col-oration of fixed cells showed that BHAE induced cells density and morphological changes. Moreover, our results showed that the treatment induced elevation of MDA, cytochrome c, p38MAPK and NF-kB level, but did not affect Akt and Erk 1/2 rates. We have also observed that the treatment with BHAE enhanced the expression of p53. Taken together, our results suggest that the BHAE triggered cell death by activation of apoptosis through ROS induction.