Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus (greater celandine). It is a potent, selective, and cell-permeable protein kinase Cinhibitorin vitro.[1] And an efficacious antagonist of G-protein-coupledCB1 receptors.[2] This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally, this molecule has two distinct conformations, one being a positively charged iminium form, and the other being an uncharged form, a pseudo-base.[3]
Chelerythrine is a potent antibacterial agent that has aided in dealing with the emergence of antibacterial resistant bacteria. This molecule has the ability to disrupt a bacteria's cell wall and cell membrane, as well as preventing bacterial growth, all of which contribute to bacterial death.[6]
Cellular apoptosisedit
Studies have shown that chelerythrine inhibits SERCA activity, more importantly the concentration needed to inhibit this enzyme is within range to that needed to inhibit protein kinase C. The negative regulation of SERCA activity results in accumulation of calcium ions in the cytoplasm, leading to the forced influx of calcium ions to the mitochondria. High calcium ion concentration in the mitochondria greatly alters its normal activity and leads to apoptosis signaling, and eventually cellular destruction. Other cellular transporters, like the PMCA, have also been shown to be negatively regulated by chelerythrine, preventing PMCA to effectively take out calcium ions from inside the cell. This further contributes to the loss of calcium ion balance within the cell and eventual cell death.[7][8] In triple-negative breast cancer cells, this molecule is found to induce apoptosis. Nuclear fragmentation and chromatin condensation is observed, which is indicative of apoptosis. [9]
Otheredit
Previous studies have showcased chelerythrine's ability to inhibit, or delay, cell proliferation, allowing it to be used to combat cancerous cells and promote cellular apoptosis, both in vivo and in vitro.[10][11] However, further studies of this alkaloid have revealed that it has low selectivity and it can also promote cellular apoptosis of non-cancerous cells, thus displaying cytotoxic behavior.[12][13][14] The creation of chelerythrine analogs have helped exploit this molecule's anticancer capabilities, while lessening its cytotoxic effects on non-cancerous cells. These novel analogs have been modified to have increased specificity for cancerous cells, thus decreasing cytotoxic effects and non-cancerous cell apoptosis.[15]
Anti-cancer mechanismsedit
Depending on the form of cancer, chelerythrine can exhibit different effects on tumor cells, leading to inhibition of tumor growth. These mechanisms include inducing apoptosis, arrest of the cell cycle, promoting autophagy of cancerous cells, and the inhibition of telomerase. It has been found to be a possible anti-cancer agent for liver, gastric, breast, renal, and cervical cancers.[16] Despite these claims, it is important to note that the related compound sanguinarine is associated with severe adverse effects. This is insufficient evidence to endorse the usage of chelerythrine present in botanical products as a cancer treatment.
Role as a protein kinase C inhibitoredit
Studies show that chelerythrine is a specific and potent protein kinase C inhibitor. Due to its inhibitory effects on protein kinase C, it has been found of use against triple-negative breast cancer. By inhibiting protein kinase C, signaling pathways are disrupted, inducing cell cycle arrest.[17]
^Dhopeshwarkar, Amey S.; Jain, Saurabh; Liao, Chengyong; Ghose, Sudip K.; Bisset, Kathleen M.; Nicholson, Russell A. (2011-03-01). "The actions of benzophenanthridine alkaloids, piperonyl butoxide and (S)-methoprene at the G-protein coupled cannabinoid CB₁ receptor in vitro". European Journal of Pharmacology. 654 (1): 26–32. doi:10.1016/j.ejphar.2010.11.033. ISSN 1879-0712. PMID 21172340.
^Dostál, Jiří; Táborská, Eva; Slavík, Jiří; Potáček, Milan; de Hoffmann, Edmond (May 1995). "Structure of Chelerythrine Base". Journal of Natural Products. 58 (5): 723–729. doi:10.1021/np50119a010. ISSN 0163-3864.
^Tavares, Luciana de C; Zanon, Graciane; Weber, Andréia D.; et al. (2014). "<Structure-activity relationship of benzophenanthridine alkaloids from Zanthoxylum rhoifolium having antimicrobial activity>". PLOS ONE. 9 (5): e97000. Bibcode:2014PLoSO...997000T. doi:10.1371/journal.pone.0097000. PMC4019524. PMID 24824737.
^He, Nan; Wang, Peiqing; Wang, Pengyu; Ma, Changyang; Kang, Wenyi (2018-09-26). "Antibacterial mechanism of chelerythrine isolated from root of Toddalia asiatica (Linn) Lam". BMC Complementary and Alternative Medicine. 18 (1): 261. doi:10.1186/s12906-018-2317-3. ISSN 1472-6882. PMC6158911. PMID 30257662.
^Saavedra, Ana; Fernández-García, Sara; Cases, Silvia; Puigdellívol, Mar; Alcalá-Vida, Rafael; Martín-Flores, Núria; Alberch, Jordi; Ginés, Silvia; Malagelada, Cristina; Pérez-Navarro, Esther (April 2017). "Chelerythrine promotes Ca2+-dependent calpain activation in neuronal cells in a PKC-independent manner". Biochimica et Biophysica Acta (BBA) - General Subjects. 1861 (4): 922–935. doi:10.1016/j.bbagen.2017.01.021. ISSN 0304-4165. PMID 28130160.
^Vieira, Saulo Martins; de Oliveira, Vanessa Honorato; Valente, Raphael do Carmo; Moreira, Otacílio da Cruz; Fontes, Carlos Frederico Leite; Mignaco, Julio Alberto (2015-03-15). "Chelerythrine inhibits the sarco/endoplasmic reticulum Ca(2+)-ATPase and results in cell Ca(2+) imbalance". Archives of Biochemistry and Biophysics. 570: 58–65. doi:10.1016/j.abb.2015.02.019. ISSN 1096-0384. PMID 25721495.
^Lin, Wanjun; Huang, Jiajun; Yuan, Zhongwen; Feng, Senling; Xie, Ying; Ma, Wenzhe (2017-05-17). "Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells". Scientific Reports. 7 (1): 2022. doi:10.1038/s41598-017-02222-0. ISSN 2045-2322. PMC5435721. PMID 28515445. S2CID 20299447.
^Kumar, Sanjay; Tomar, Munendra Singh; Acharya, Arbind (October 2015). "Chelerythrine delayed tumor growth and increased survival duration of Dalton's lymphoma bearing BALB/c H(2d) mice by activation of NK cells in vivo". Journal of Cancer Research and Therapeutics. 11 (4): 904–910. doi:10.4103/0973-1482.143342. ISSN 1998-4138. PMID 26881539.
^Vieira, Saulo Martins; de Oliveira, Vanessa Honorato; Valente, Raphael do Carmo; Moreira, Otacílio da Cruz; Fontes, Carlos Frederico Leite; Mignaco, Julio Alberto (2015-03-15). "Chelerythrine inhibits the sarco/endoplasmic reticulum Ca(2+)-ATPase and results in cell Ca(2+) imbalance". Archives of Biochemistry and Biophysics. 570: 58–65. doi:10.1016/j.abb.2015.02.019. ISSN 1096-0384. PMID 25721495.
^Shen, Yizhong; Zhu, Chunlei; Wang, Yaping; Xu, Jingjing; Xue, Ruyu; Ji, Fuyun; Wu, Yiwei; Wu, Zeyu; Zhang, Wencheng; Zheng, Zhi; Ye, Yingwang (2020-01-01). "Evaluation the binding of chelerythrine, a potentially harmful toxin, with bovine serum albumin". Food and Chemical Toxicology. 135: 110933. doi:10.1016/j.fct.2019.110933. ISSN 0278-6915. PMID 31682930.
^Zhang, Zhengfu; Guo, Ying; Zhang, Lingwei; Zhang, Jianbin; Wei, Xionghui (2012-10-01). "Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC-823 cells". Acta Pharmaceutica Sinica B. 2 (5): 464–471. doi:10.1016/j.apsb.2011.12.013. ISSN 2211-3835.
^Yang, Rosania; Tavares, Maurício T.; Teixeira, Sarah F.; Azevedo, Ricardo A.; C Pietro, Diego; Fernandes, Thais B.; Ferreira, Adilson K.; Trossini, Gustavo H. G.; Barbuto, José A. M.; Parise-Filho, Roberto (1 October 2016). "Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells". Bioorganic & Medicinal Chemistry. 24 (19): 4600–4610. doi:10.1016/j.bmc.2016.07.065. ISSN 1464-3391. PMID 27561984.
^Chen, Nianzhi; Qi, Yulin; Ma, Xiao; Xiao, Xiaolin; Liu, Qingsong; Xia, Ting; Xiang, Juyi; Zeng, Jinhao; Tang, Jianyuan (2022). "Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine". Frontiers in Pharmacology. 13: 906301. doi:10.3389/fphar.2022.906301. ISSN 1663-9812. PMC9198297. PMID 35721116.
^Lin, Wanjun; Huang, Jiajun; Yuan, Zhongwen; Feng, Senling; Xie, Ying; Ma, Wenzhe (2017-05-17). "Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells". Scientific Reports. 7 (1): 2022. doi:10.1038/s41598-017-02222-0. ISSN 2045-2322. PMC5435721. PMID 28515445. S2CID 20299447.
November 02, 2023
chelerythrine, benzophenanthridine, alkaloid, present, plant, chelidonium, majus, greater, celandine, potent, selective, cell, permeable, protein, kinase, inhibitor, vitro, efficacious, antagonist, protein, coupled, receptors, this, molecule, also, exhibits, a. Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus greater celandine It is a potent selective and cell permeable protein kinase C inhibitor in vitro 1 And an efficacious antagonist of G protein coupled CB1 receptors 2 This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer Structurally this molecule has two distinct conformations one being a positively charged iminium form and the other being an uncharged form a pseudo base 3 Chelerythrine NamesPreferred IUPAC name 1 2 Dimethoxy 12 methyl 9H 1 3 benzodioxolo 5 6 c phenanthridin 12 iumIdentifiersCAS Number 34316 15 9 N3D model JSmol Interactive imageChEBI CHEBI 78373 NChEMBL ChEMBL258893 NChemSpider 2602 YECHA InfoCard 100 047 194IUPHAR BPS 5953PubChem CID 2703UNII E3B045W6X0 YCompTox Dashboard EPA DTXSID20861211InChI InChI 1S C21H18NO4 c1 22 10 16 13 6 7 17 23 2 21 16 24 3 14 5 4 12 8 18 19 26 11 25 18 9 15 12 20 14 22 h4 10H 11H2 1 3H3 q 1 YKey LLEJIEBFSOEYIV UHFFFAOYSA N YInChI 1 C21H18NO4 c1 22 10 16 13 6 7 17 23 2 21 16 24 3 14 5 4 12 8 18 19 26 11 25 18 9 15 12 20 14 22 h4 10H 11H2 1 3H3 q 1Key LLEJIEBFSOEYIV UHFFFAOYAPSMILES O1c3c OC1 cc2ccc4c5c c n c4c2c3 C c OC c OC cc5PropertiesChemical formula C 21H 18N O 4Molar mass 348 378 g mol 1Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references It is also found in the plants Zanthoxylum clava herculis and Zanthoxylum rhoifolium exhibiting antibacterial activity against Staphylococcus aureus and other human pathogens 4 5 Contents 1 Research 1 1 Antibacterial agent 1 2 Cellular apoptosis 1 3 Other 1 4 Anti cancer mechanisms 1 5 Role as a protein kinase C inhibitor 2 ReferencesResearch editAntibacterial agent edit Chelerythrine is a potent antibacterial agent that has aided in dealing with the emergence of antibacterial resistant bacteria This molecule has the ability to disrupt a bacteria s cell wall and cell membrane as well as preventing bacterial growth all of which contribute to bacterial death 6 Cellular apoptosis edit Studies have shown that chelerythrine inhibits SERCA activity more importantly the concentration needed to inhibit this enzyme is within range to that needed to inhibit protein kinase C The negative regulation of SERCA activity results in accumulation of calcium ions in the cytoplasm leading to the forced influx of calcium ions to the mitochondria High calcium ion concentration in the mitochondria greatly alters its normal activity and leads to apoptosis signaling and eventually cellular destruction Other cellular transporters like the PMCA have also been shown to be negatively regulated by chelerythrine preventing PMCA to effectively take out calcium ions from inside the cell This further contributes to the loss of calcium ion balance within the cell and eventual cell death 7 8 In triple negative breast cancer cells this molecule is found to induce apoptosis Nuclear fragmentation and chromatin condensation is observed which is indicative of apoptosis 9 Other edit Previous studies have showcased chelerythrine s ability to inhibit or delay cell proliferation allowing it to be used to combat cancerous cells and promote cellular apoptosis both in vivo and in vitro 10 11 However further studies of this alkaloid have revealed that it has low selectivity and it can also promote cellular apoptosis of non cancerous cells thus displaying cytotoxic behavior 12 13 14 The creation of chelerythrine analogs have helped exploit this molecule s anticancer capabilities while lessening its cytotoxic effects on non cancerous cells These novel analogs have been modified to have increased specificity for cancerous cells thus decreasing cytotoxic effects and non cancerous cell apoptosis 15 Anti cancer mechanisms edit Depending on the form of cancer chelerythrine can exhibit different effects on tumor cells leading to inhibition of tumor growth These mechanisms include inducing apoptosis arrest of the cell cycle promoting autophagy of cancerous cells and the inhibition of telomerase It has been found to be a possible anti cancer agent for liver gastric breast renal and cervical cancers 16 Despite these claims it is important to note that the related compound sanguinarine is associated with severe adverse effects This is insufficient evidence to endorse the usage of chelerythrine present in botanical products as a cancer treatment Role as a protein kinase C inhibitor edit Studies show that chelerythrine is a specific and potent protein kinase C inhibitor Due to its inhibitory effects on protein kinase C it has been found of use against triple negative breast cancer By inhibiting protein kinase C signaling pathways are disrupted inducing cell cycle arrest 17 References edit Chelerythrine Chloride from Fermentek Dhopeshwarkar Amey S Jain Saurabh Liao Chengyong Ghose Sudip K Bisset Kathleen M Nicholson Russell A 2011 03 01 The actions of benzophenanthridine alkaloids piperonyl butoxide and S methoprene at the G protein coupled cannabinoid CB receptor in vitro European Journal of Pharmacology 654 1 26 32 doi 10 1016 j ejphar 2010 11 033 ISSN 1879 0712 PMID 21172340 Dostal Jiri Taborska Eva Slavik Jiri Potacek Milan de Hoffmann Edmond May 1995 Structure of Chelerythrine Base Journal of Natural Products 58 5 723 729 doi 10 1021 np50119a010 ISSN 0163 3864 Gibbons Simon Leimkugel Julia Oluwatuyi Moyo et al 2003 lt Activity of Zanthoxylum clava herculis extracts against multi drug resistant methicillin resistant Staphylococcus aureus mdr MRSA gt Phytotherapy Research 17 3 274 275 doi 10 1002 ptr 1112 PMID 12672160 S2CID 32722743 Tavares Luciana de C Zanon Graciane Weber Andreia D et al 2014 lt Structure activity relationship of benzophenanthridine alkaloids from Zanthoxylum rhoifolium having antimicrobial activity gt PLOS ONE 9 5 e97000 Bibcode 2014PLoSO 997000T doi 10 1371 journal pone 0097000 PMC 4019524 PMID 24824737 He Nan Wang Peiqing Wang Pengyu Ma Changyang Kang Wenyi 2018 09 26 Antibacterial mechanism of chelerythrine isolated from root of Toddalia asiatica Linn Lam BMC Complementary and Alternative Medicine 18 1 261 doi 10 1186 s12906 018 2317 3 ISSN 1472 6882 PMC 6158911 PMID 30257662 Saavedra Ana Fernandez Garcia Sara Cases Silvia Puigdellivol Mar Alcala Vida Rafael Martin Flores Nuria Alberch Jordi Gines Silvia Malagelada Cristina Perez Navarro Esther April 2017 Chelerythrine promotes Ca2 dependent calpain activation in neuronal cells in a PKC independent manner Biochimica et Biophysica Acta BBA General Subjects 1861 4 922 935 doi 10 1016 j bbagen 2017 01 021 ISSN 0304 4165 PMID 28130160 Vieira Saulo Martins de Oliveira Vanessa Honorato Valente Raphael do Carmo Moreira Otacilio da Cruz Fontes Carlos Frederico Leite Mignaco Julio Alberto 2015 03 15 Chelerythrine inhibits the sarco endoplasmic reticulum Ca 2 ATPase and results in cell Ca 2 imbalance Archives of Biochemistry and Biophysics 570 58 65 doi 10 1016 j abb 2015 02 019 ISSN 1096 0384 PMID 25721495 Lin Wanjun Huang Jiajun Yuan Zhongwen Feng Senling Xie Ying Ma Wenzhe 2017 05 17 Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple negative breast cancer cells Scientific Reports 7 1 2022 doi 10 1038 s41598 017 02222 0 ISSN 2045 2322 PMC 5435721 PMID 28515445 S2CID 20299447 Chen Xiao Meng Zhang Meng Fan Peng Li Qin Yu Hua Zhao Hong Wei June 2016 Chelerythrine chloride induces apoptosis in renal cancer HEK 293 and SW 839 cell lines Oncology Letters 11 6 3917 3924 doi 10 3892 ol 2016 4520 ISSN 1792 1074 PMC 4888265 PMID 27313717 Kumar Sanjay Tomar Munendra Singh Acharya Arbind October 2015 Chelerythrine delayed tumor growth and increased survival duration of Dalton s lymphoma bearing BALB c H 2d mice by activation of NK cells in vivo Journal of Cancer Research and Therapeutics 11 4 904 910 doi 10 4103 0973 1482 143342 ISSN 1998 4138 PMID 26881539 Vieira Saulo Martins de Oliveira Vanessa Honorato Valente Raphael do Carmo Moreira Otacilio da Cruz Fontes Carlos Frederico Leite Mignaco Julio Alberto 2015 03 15 Chelerythrine inhibits the sarco endoplasmic reticulum Ca 2 ATPase and results in cell Ca 2 imbalance Archives of Biochemistry and Biophysics 570 58 65 doi 10 1016 j abb 2015 02 019 ISSN 1096 0384 PMID 25721495 Shen Yizhong Zhu Chunlei Wang Yaping Xu Jingjing Xue Ruyu Ji Fuyun Wu Yiwei Wu Zeyu Zhang Wencheng Zheng Zhi Ye Yingwang 2020 01 01 Evaluation the binding of chelerythrine a potentially harmful toxin with bovine serum albumin Food and Chemical Toxicology 135 110933 doi 10 1016 j fct 2019 110933 ISSN 0278 6915 PMID 31682930 Zhang Zhengfu Guo Ying Zhang Lingwei Zhang Jianbin Wei Xionghui 2012 10 01 Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC 823 cells Acta Pharmaceutica Sinica B 2 5 464 471 doi 10 1016 j apsb 2011 12 013 ISSN 2211 3835 Yang Rosania Tavares Mauricio T Teixeira Sarah F Azevedo Ricardo A C Pietro Diego Fernandes Thais B Ferreira Adilson K Trossini Gustavo H G Barbuto Jose A M Parise Filho Roberto 1 October 2016 Toward chelerythrine optimization Analogues designed by molecular simplification exhibit selective growth inhibition in non small cell lung cancer cells Bioorganic amp Medicinal Chemistry 24 19 4600 4610 doi 10 1016 j bmc 2016 07 065 ISSN 1464 3391 PMID 27561984 Chen Nianzhi Qi Yulin Ma Xiao Xiao Xiaolin Liu Qingsong Xia Ting Xiang Juyi Zeng Jinhao Tang Jianyuan 2022 Rediscovery of Traditional Plant Medicine An Underestimated Anticancer Drug of Chelerythrine Frontiers in Pharmacology 13 906301 doi 10 3389 fphar 2022 906301 ISSN 1663 9812 PMC 9198297 PMID 35721116 Lin Wanjun Huang Jiajun Yuan Zhongwen Feng Senling Xie Ying Ma Wenzhe 2017 05 17 Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple negative breast cancer cells Scientific Reports 7 1 2022 doi 10 1038 s41598 017 02222 0 ISSN 2045 2322 PMC 5435721 PMID 28515445 S2CID 20299447 Retrieved from https en wikipedia org w index php title Chelerythrine amp oldid 1182187450, wikipedia, wiki, book, books, library,
