Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects

In Press, (this is not the final "Version of Record"). Available online 07 August, 2024
Author(s): El Abbassi Ayoub*, Zineb Azoubi, Zougagh Nadia, Mouslim Assia and Menggad Mohammed
Published on: 07 August, 2024

DOI: 10.2174/0118715206314212240805105735

Price: $95

Abstract

The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.

[1]
Williamson, N.R.; Fineran, P.C.; Leeper, F.J.; Salmond, G.P.C. The biosynthesis and regulation of bacterial prodiginines. Nat. Rev. Microbiol., 2006, 4(12), 887-899.
[http://dx.doi.org/10.1038/nrmicro1531] [PMID: 17109029]
[2]
Ullah, A.; Aziz, T.; Ullah, N.; Nawaz, T. Molecular mechanisms of sanguinarine in cancer prevention and treatment. Anticancer. Agents Med. Chem., 2023, 23(7), 765-778.
[http://dx.doi.org/10.2174/1871520622666220831124321] [PMID: 36045531]
[3]
Ullah, A.; Razzaq, A.; Alfaifi, M.Y.; Elbehairi, S.E.I.; Menaa, F.; Ullah, N.; Shehzadi, S.; Nawaz, T.; Iqbal, H. Sanguinarine attenuates lung cancer progression via oxidative stress-induced cell apoptosis. Curr. Mol. Pharmacol., 2024, 17, e18761429269383.
[http://dx.doi.org/10.2174/0118761429269383231119062233] [PMID: 38389415]
[4]
Wang, Z.; Li, B.; Zhou, L.; Yu, S.; Su, Z.; Song, J.; Sun, Q.; Sha, O.; Wang, X.; Jiang, W.; Willert, K.; Wei, L.; Carson, D.A.; Lu, D. Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells. Proc. Natl. Acad. Sci. , 2016, 113(46), 13150-13155.
[http://dx.doi.org/10.1073/pnas.1616336113] [PMID: 27799526]
[5]
Kapoor, R.; Saini, A.; Sharma, D. Indispensable role of microbes in anticancer drugs and discovery trends. Appl. Microbiol. Biotechnol., 2022, 106(13-16), 4885-4906.
[http://dx.doi.org/10.1007/s00253-022-12046-2] [PMID: 35819512]
[6]
Law, J.W.F.; Law, L.N.S.; Letchumanan, V.; Tan, L.T.H.; Wong, S.H.; Chan, K.G.; Ab Mutalib, N.S.; Lee, L.H. Anticancer drug discovery from microbial sources: the unique mangrove streptomycetes. Molecules, 2020, 25(22), 5365.
[http://dx.doi.org/10.3390/molecules25225365] [PMID: 33212836]
[7]
Baindara, P.; Mandal, S.M. Bacteria and bacterial anticancer agents as a promising alternative for cancer therapeutics. Biochimie, 2020, 177, 164-189.
[http://dx.doi.org/10.1016/j.biochi.2020.07.020] [PMID: 32827604]
[8]
Rivankar, S. An overview of doxorubicin formulations in cancer therapy. J. Cancer Res. Ther., 2014, 10(4), 853-858.
[http://dx.doi.org/10.4103/0973-1482.139267] [PMID: 25579518]
[9]
Takeuchi, T. Antitumor antibiotics discovered and studied at the Institute of Microbial Chemistry. J. Cancer Res. Clin. Oncol., 1995, 121(9-10), 505-510.
[http://dx.doi.org/10.1007/BF01197761] [PMID: 7559728]
[10]
Hollstein, U. Actinomycin. Chemistry and mechanism of action. Chem. Rev., 1974, 74(6), 625-652.
[http://dx.doi.org/10.1021/cr60292a002]
[11]
Ramos, A.; Sadeghi, S.; Tabatabaeian, H. Battling chemoresistance in cancer: root causes and strategies to uproot them. Int. J. Mol. Sci., 2021, 22(17), 9451.
[http://dx.doi.org/10.3390/ijms22179451] [PMID: 34502361]
[12]
Lazaro, J.E.H.; Nitcheu, J.; Predicala, R.Z.; Mangalindan, G.C.; Nesslany, F.; Marzin, D.; Concepcion, G.P.; Diquet, B. Heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro. J. Nat. Toxins, 2002, 11(4), 367-377.
[PMID: 12503881]
[13]
Yip, C.H.; Mahalingam, S.; Wan, K.L.; Nathan, S. Prodigiosin inhibits bacterial growth and virulence factors as a potential physiological response to interspecies competition. PLoS One, 2021, 16(6), e0253445.
[http://dx.doi.org/10.1371/journal.pone.0253445] [PMID: 34161391]
[14]
Han, S.B.; Kim, H.M.; Kim, Y.H.; Lee, C.W.; Jang, E.S.; Son, K.H.; Kim, S.U.; Kim, Y.K. T-cell specific immunosuppression by prodigiosin isolated from Serratia marcescens. Int. J. Immunopharmacol., 1998, 20(1-3), 1-13.
[http://dx.doi.org/10.1016/S0192-0561(97)00062-3] [PMID: 9717078]
[15]
Darshan, N.; Manonmani, H.K. Prodigiosin and its potential applications. J. Food Sci. Technol., 2015, 52(9), 5393-5407.
[http://dx.doi.org/10.1007/s13197-015-1740-4] [PMID: 26344956]
[16]
Hu, D.X.; Withall, D.M.; Challis, G.L.; Thomson, R.J. Structure, chemical synthesis, and biosynthesis of prodiginine natural products. Chem. Rev., 2016, 116(14), 7818-7853.
[http://dx.doi.org/10.1021/acs.chemrev.6b00024] [PMID: 27314508]
[17]
Mouslim, A.; Menggad, S.; Habti, N.; Affar, E.B.; Menggad, M. Antiproliferative effect on cancer cells of novel pink red-like pigments and derivatives produced by Streptomyces coelicoflavus strains. J. Cancer Res., 2019, 7(1), 27-33.
[18]
Kim, D.; Lee, J.S.; Park, Y.K.; Kim, J.F.; Jeong, H.; Oh, T.K.; Kim, B.S.; Lee, C.H. Biosynthesis of antibiotic prodiginines in the marine bacterium Hahella chejuensis KCTC 2396. J. Appl. Microbiol., 2007, 102(4), 937-944.
[PMID: 17381736]
[19]
Lee, J.S.; Kim, Y.S.; Park, S.; Kim, J.; Kang, S.J.; Lee, M.H.; Ryu, S.; Choi, J.M.; Oh, T.K.; Yoon, J.H. Exceptional production of both prodigiosin and cycloprodigiosin as major metabolic constituents by a novel marine bacterium, Zooshikella rubidus S1-1. Appl. Environ. Microbiol., 2011, 77(14), 4967-4973.
[http://dx.doi.org/10.1128/AEM.01986-10] [PMID: 21642414]
[20]
Cerdeño, A.M.; Bibb, M.J.; Challis, G.L. Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes. Chem. Biol., 2001, 8(8), 817-829.
[http://dx.doi.org/10.1016/S1074-5521(01)00054-0] [PMID: 11514230]
[21]
Jia, X. Identification of essential genes associated with prodigiosin production in serratia marcescens FZSF02. Front. Microbiol., 2021, 12, 705853.
[http://dx.doi.org/10.3389/fmicb.2021.705853]
[22]
Lu, Y.; Liu, D.; Jiang, R.; Li, Z.; Gao, X. Prodigiosin: unveiling the crimson wonder – a comprehensive journey from diverse bioactivity to synthesis and yield enhancement. Front. Microbiol., 2024, 15, 1412776.
[http://dx.doi.org/10.3389/fmicb.2024.1412776] [PMID: 38903802]
[23]
Williamson, N.R.; Simonsen, H.T.; Ahmed, R.A.A.; Goldet, G.; Slater, H.; Woodley, L.; Leeper, F.J.; Salmond, G.P.C. Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol. Microbiol., 2005, 56(4), 971-989.
[http://dx.doi.org/10.1111/j.1365-2958.2005.04602.x] [PMID: 15853884]
[24]
Li, P.; He, S.; Zhang, X.; Gao, Q.; Liu, Y.; Liu, L. Structures, biosynthesis, and bioactivities of prodiginine natural products. Appl. Microbiol. Biotechnol., 2022, 106(23), 7721-7735.
[http://dx.doi.org/10.1007/s00253-022-12245-x] [PMID: 36319792]
[25]
Feitelson, J.S.; Malpartida, F.; Hopwood, D.A. Genetic and biochemical characterization of the red gene cluster of Streptomyces coelicolor A3(2). Microbiology, 1985, 131(9), 2431-2441.
[http://dx.doi.org/10.1099/00221287-131-9-2431] [PMID: 2999302]
[26]
Gristwood, T.; McNeil, M.B.; Clulow, J.S.; Salmond, G.P.C.; Fineran, P.C. PigS and PigP regulate prodigiosin biosynthesis in Serratia via differential control of divergent operons, which include predicted transporters of sulfur-containing molecules. J. Bacteriol., 2011, 193(5), 1076-1085.
[http://dx.doi.org/10.1128/JB.00352-10] [PMID: 21183667]
[27]
Kim, D. Analysis of a prodigiosin biosynthetic gene cluster from the marine bacterium Hahella chejuensis KCTC 2396. J. Microbiol. Biotechnol., 2006, 16(12), 1912.
[28]
Kwon, S.K.; Park, Y.K.; Kim, J.F. Genome-wide screening and identification of factors affecting the biosynthesis of prodigiosin by Hahella chejuensis, using Escherichia coli as a surrogate host. Appl. Environ. Microbiol., 2010, 76(5), 1661-1668.
[http://dx.doi.org/10.1128/AEM.01468-09] [PMID: 20038694]
[29]
Harris, A.K.P.; Williamson, N.R.; Slater, H.; Cox, A.; Abbasi, S.; Foulds, I.; Simonsen, H.T.; Leeper, F.J.; Salmond, G.P.C. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology, 2004, 150(11), 3547-3560.
[http://dx.doi.org/10.1099/mic.0.27222-0] [PMID: 15528645]
[30]
Borah, S.; Melvin, M.S.; Lindquist, N.; Manderville, R.A. Copper-mediated nuclease activity of a tambjamine alkaloid. J. Am. Chem. Soc., 1998, 120(19), 4557-4562.
[http://dx.doi.org/10.1021/ja9729746]
[31]
Zhao, W.; Gao, D.; Ning, L.; Jiang, Y.; Li, Z.; Huang, B.; Chen, A.; Wang, C.; Liu, Y. Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway. Sci. Rep., 2022, 12(1), 18527.
[http://dx.doi.org/10.1038/s41598-022-23186-w] [PMID: 36323805]
[32]
Anwar, M.M.; Shalaby, M.; Embaby, A.M.; Saeed, H.; Agwa, M.M.; Hussein, A. Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights. Sci. Rep., 2020, 10(1), 14706.
[http://dx.doi.org/10.1038/s41598-020-71157-w] [PMID: 32895397]
[33]
Melvin, M.S.; Ferguson, D.C.; Lindquist, N.; Manderville, R.A. DNA binding by 4-methoxypyrrolic natural products. Preference for intercalation at AT sites by tambjamine E and prodigiosin. J. Org. Chem., 1999, 64(18), 6861-6869.
[http://dx.doi.org/10.1021/jo990944a] [PMID: 11674696]
[34]
Melvin, M.S.; Tomlinson, J.T.; Saluta, G.R.; Kucera, G.L.; Lindquist, N.; Manderville, R.A. Double-strand DNA cleavage by copper⊙ prodigiosin. J. Am. Chem. Soc., 2000, 122(26), 6333-6334.
[http://dx.doi.org/10.1021/ja0000798]
[35]
Melvin, M.S.; Wooton, K.E.; Rich, C.C.; Saluta, G.R.; Kucera, G.L.; Lindquist, N.; Manderville, R.A. Copper-nuclease efficiency correlates with cytotoxicity for the 4-methoxypyrrolic natural products. J. Inorg. Biochem., 2001, 87(3), 129-135.
[http://dx.doi.org/10.1016/S0162-0134(01)00338-5] [PMID: 11730894]
[36]
Montaner, B.; Castillo-Ávila, W.; Martinell, M.; Öllinger, R.; Aymami, J.; Giralt, E.; Pérez-Tomás, R. DNA interaction and dual topoisomerase I and II inhibition properties of the anti-tumor drug prodigiosin. Toxicol. Sci., 2005, 85(2), 870-879.
[http://dx.doi.org/10.1093/toxsci/kfi149] [PMID: 15788728]
[37]
Nguyen, M.; Marcellus, R.C.; Roulston, A.; Watson, M.; Serfass, L.; Murthy Madiraju, S.R.; Goulet, D.; Viallet, J.; Bélec, L.; Billot, X.; Acoca, S.; Purisima, E.; Wiegmans, A.; Cluse, L.; Johnstone, R.W.; Beauparlant, P.; Shore, G.C. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad. Sci., 2007, 104(49), 19512-19517.
[http://dx.doi.org/10.1073/pnas.0709443104] [PMID: 18040043]
[38]
Hassankhani, R.; Sam, M.R.; Esmaeilou, M.; Ahangar, P. Prodigiosin isolated from cell wall of Serratia marcescens alters expression of apoptosis-related genes and increases apoptosis in colorectal cancer cells. Med. Oncol., 2015, 32(1), 366.
[http://dx.doi.org/10.1007/s12032-014-0366-0] [PMID: 25429836]
[39]
Li, D.; Liu, J.; Wang, X.; Kong, D.; Du, W.; Li, H.; Hse, C.Y.; Shupe, T.; Zhou, D.; Zhao, K. Biological potential and mechanism of prodigiosin from Serratia marcescens subsp. lawsoniana in human choriocarcinoma and prostate cancer cell lines. Int. J. Mol. Sci., 2018, 19(11), 3465.
[http://dx.doi.org/10.3390/ijms19113465] [PMID: 30400387]
[40]
Chonghaile, T.N.; Letai, A. Mimicking the BH3 domain to kill cancer cells. Oncogene, 2008, 27(1), S149.
[http://dx.doi.org/10.1038/onc.2009.52]
[41]
Boger, D.L.; Patel, M. Total synthesis of prodigiosin, prodigiosene, and desmethoxyprodigiosin: Diels-Alder reactions of heterocyclic azadienes and development of an effective palladium(II)-promoted 2,2′-bipyrrole coupling procedure. J. Org. Chem., 1988, 53(7), 1405-1415.
[http://dx.doi.org/10.1021/jo00242a013]
[42]
Montaner, B.; Pérez-Tomás, R. The cytotoxic prodigiosin induces phosphorylation of p38-MAPK but not of SAPK/JNK. Toxicol. Lett., 2002, 129(1-2), 93-98.
[http://dx.doi.org/10.1016/S0378-4274(01)00477-5] [PMID: 11879978]
[43]
Lu, C.H.; Lin, S.C.; Yang, S.Y.; Pan, M.Y.; Lin, Y.W.; Hsu, C.Y.; Wei, Y.H.; Chang, J.S.; Chang, C.C. Prodigiosin-induced cytotoxicity involves RAD51 down-regulation through the JNK and p38 MAPK pathways in human breast carcinoma cell lines. Toxicol. Lett., 2012, 212(1), 83-89.
[http://dx.doi.org/10.1016/j.toxlet.2012.05.002] [PMID: 22579953]
[44]
Forgac, M. Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 917-929.
[http://dx.doi.org/10.1038/nrm2272] [PMID: 17912264]
[45]
Nilsson, C.; Johansson, U.; Johansson, A.C.; Kågedal, K.; Öllinger, K. Cytosolic acidification and lysosomal alkalinization during TNF-α induced apoptosis in U937 cells. Apoptosis, 2006, 11(7), 1149-1159.
[http://dx.doi.org/10.1007/s10495-006-7108-5] [PMID: 16699952]
[46]
Lagadic-Gossmann, D.; Huc, L.; Lecureur, V. Alterations of intracellular pH homeostasis in apoptosis: origins and roles. Cell Death Differ., 2004, 11(9), 953-961.
[http://dx.doi.org/10.1038/sj.cdd.4401466] [PMID: 15195071]
[47]
Gottlieb, R.A. Cell acidification in apoptosis. Apoptosis, 1996, 1(1), 40-48.
[http://dx.doi.org/10.1007/BF00142077]
[48]
Stransky, L.; Cotter, K.; Forgac, M. The function of V-ATPases in cancer. Physiol. Rev., 2016, 96(3), 1071-1091.
[http://dx.doi.org/10.1152/physrev.00035.2015] [PMID: 27335445]
[49]
Sato, T.; Konno, H.; Tanaka, Y.; Kataoka, T.; Nagai, K.; Wasserman, H.H.; Ohkuma, S. Prodigiosins as a new group of H+/Cl- symporters that uncouple proton translocators. J. Biol. Chem., 1998, 273(34), 21455-21462.
[http://dx.doi.org/10.1074/jbc.273.34.21455] [PMID: 9705273]
[50]
Francisco, R.; Pérez-Tomás, R.; Gimènez-Bonafé, P.; Soto-Cerrato, V.; Giménez-Xavier, P.; Ambrosio, S. Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines. Eur. J. Pharmacol., 2007, 572(2-3), 111-119.
[http://dx.doi.org/10.1016/j.ejphar.2007.06.054] [PMID: 17678643]
[51]
Sessler, J.L.; Eller, L.R.; Cho, W.S.; Nicolaou, S.; Aguilar, A.; Lee, J.T.; Lynch, V.M.; Magda, D.J. Synthesis, anion-binding properties, and in vitro anticancer activity of prodigiosin analogues. Angew. Chem. Int. Ed., 2005, 44(37), 5989-5992.
[http://dx.doi.org/10.1002/anie.200501740] [PMID: 16114075]
[52]
Seganish, J.L.; Davis, J.T. Prodigiosin is a chloride carrier that can function as an anion exchanger. Chem. Commun. , 2005, (46), 5781-5783.
[http://dx.doi.org/10.1039/b511847f] [PMID: 16307144]
[53]
Liu, P.; Wang, Y.; Qi, X.; Gu, Q.; Geng, M.; Li, J. Undecylprodigiosin induced apoptosis in P388 cancer cells is associated with its binding to ribosome. PLoS One, 2013, 8(6), e65381.
[http://dx.doi.org/10.1371/journal.pone.0065381] [PMID: 23799011]
[54]
Melvin, M.S.; Calcutt, M.W.; Noftle, R.E.; Manderville, R.A. Influence of the a-ring on the redox and nuclease properties of the prodigiosins: importance of the bipyrrole moiety in oxidative DNA cleavage. Chem. Res. Toxicol., 2002, 15(5), 742-748.
[http://dx.doi.org/10.1021/tx025508p] [PMID: 12018997]
[55]
Povirk, L.F.; Hogan, M.; Dattagupta, N. Binding of bleomycin to DNA: intercalation of the bithiazole rings. Biochemistry, 1979, 18(1), 96-101.
[http://dx.doi.org/10.1021/bi00568a015] [PMID: 84680]
[56]
Paul, V.J.; Lindquist, N.; Fenical, W. Chemical defenses of the tropical ascidian Atapozoa sp. and its nudibranch predators Nembrotha spp. Mar. Ecol. Prog. Ser., 1990, 59(1/2), 109-118.
[http://dx.doi.org/10.3354/meps059109]
[57]
Wasserman, H.H.; Friedland, D.J.; Morrison, D.A. A novel dipyrrolyldipyrromethene prodigiosin analog from. Tetrahedron Lett., 1968, 9(6), 641-644.
[http://dx.doi.org/10.1016/S0040-4039(00)75602-4] [PMID: 4867609]
[58]
De Rosa, M.; Johnson, S.A.; Opresko, P.L. Roles for the 8-oxoguanine dna repair system in protecting telomeres from oxidative stress. Front. Cell Dev. Biol., 2021, 9, 758402.
[http://dx.doi.org/10.3389/fcell.2021.758402]
[59]
Ma, A.; Dai, X. The relationship between DNA single-stranded damage response and double-stranded damage response. Cell Cycle, 2018, 17(1), 73-79.
[http://dx.doi.org/10.1080/15384101.2017.1403681] [PMID: 29157089]
[60]
Melvin, M.S.; Tomlinson, J.T.; Park, G.; Day, C.S.; Saluta, G.R.; Kucera, G.L.; Manderville, R.A. Influence of the a-ring on the proton affinity and anticancer properties of the prodigiosins. Chem. Res. Toxicol., 2002, 15(5), 734-741.
[http://dx.doi.org/10.1021/tx025507x] [PMID: 12018996]
[61]
D’Alessio, R.; Rossi, A. Short synthesis of undecylprodigiosine. A new route to 2,2′-bipyrrolyl-pyrromethene systems. Synlett, 1996, 1996(6), 513-514.
[http://dx.doi.org/10.1055/s-1996-5485]
[62]
D’Alessio, R.; Bargiotti, A.; Carlini, O.; Colotta, F.; Ferrari, M.; Gnocchi, P.; Isetta, A.; Mongelli, N.; Motta, P.; Rossi, A.; Rossi, M.; Tibolla, M.; Vanotti, E. Synthesis and immunosuppressive activity of novel prodigiosin derivatives. J. Med. Chem., 2000, 43(13), 2557-2565.
[http://dx.doi.org/10.1021/jm001003p] [PMID: 10891115]
[63]
Hayakawa, Y.; Kawakami, K.; Seto, H.; Furihata, K. Structure of a new antibiotic, roseophilin. Tetrahedron Lett., 1992, 33(19), 2701-2704.
[http://dx.doi.org/10.1016/S0040-4039(00)79061-7]
[64]
Park, G.; Tomlinson, J.T.; Melvin, M.S.; Wright, M.W.; Day, C.S.; Manderville, R.A. Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage. Org. Lett., 2003, 5(2), 113-116.
[http://dx.doi.org/10.1021/ol027165s] [PMID: 12529118]
[65]
Park, G-S.; Tomlinson, J.T.; Misenheimer, J.A.; Kucera, G.L.; Manderville, R.A. Photo-induced cytotoxicity of prodigiosin analogues. Bull. Korean Chem. Soc., 2007, 28(1), 49-52.
[http://dx.doi.org/10.5012/bkcs.2007.28.1.049]
[66]
Meshnick, S.R. Chloroquine as intercalator: a hypothesis revived. Parasitol. Today, 1990, 6(3), 77-79.
[http://dx.doi.org/10.1016/0169-4758(90)90215-P] [PMID: 15463303]
[67]
Sevrioukova, I.F. Apoptosis-inducing factor: structure, function, and redox regulation. Antioxid. Redox Signal., 2011, 14(12), 2545-2579.
[http://dx.doi.org/10.1089/ars.2010.3445] [PMID: 20868295]
[68]
Boedtkjer, E.; Pedersen, S.F. The acidic tumor microenvironment as a driver of cancer. Annu. Rev. Physiol., 2020, 82(1), 103-126.
[http://dx.doi.org/10.1146/annurev-physiol-021119-034627] [PMID: 31730395]
[69]
Gerweck, L.E.; Seetharaman, K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res., 1996, 56(6), 1194-1198.
[PMID: 8640796]
[70]
Zhang, X.; Lin, Y.; Gillies, R.J. Tumor pH and its measurement. J. Nucl. Med., 2010, 51(8), 1167-1170.
[http://dx.doi.org/10.2967/jnumed.109.068981] [PMID: 20660380]
[71]
Baldino, C.M.; Parr, J.; Wilson, C.J.; Ng, S.C.; Yohannes, D.; Wasserman, H.H. Indoloprodigiosins from the C-10 bipyrrolic precursor: New antiproliferative prodigiosin analogs. Bioorg. Med. Chem. Lett., 2006, 16(3), 701-704.
[http://dx.doi.org/10.1016/j.bmcl.2005.10.027] [PMID: 16289814]
[72]
Regourd, J.; Al-Sheikh Ali, A.; Thompson, A. Synthesis and anti-cancer activity of C-ring-functionalized prodigiosin analogues. J. Med. Chem., 2007, 50(7), 1528-1536.
[http://dx.doi.org/10.1021/jm061088f] [PMID: 17348639]
[73]
Díaz, R.I.S.; Regourd, J.; Santacroce, P.V.; Davis, J.T.; Jakeman, D.L.; Thompson, A. Chloride anion transport and copper-mediated DNA cleavage by C-ring functionalized prodigiosenes. Chem. Commun. , 2007, (26), 2701-2703.
[http://dx.doi.org/10.1039/B701919J] [PMID: 17594025]
[74]
Kapoor, I.; Bodo, J.; Hill, B.T.; Hsi, E.D.; Almasan, A. Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance. Cell Death Dis., 2020, 11(11), 941.
[http://dx.doi.org/10.1038/s41419-020-03144-y] [PMID: 33139702]
[75]
Yuan, B.; Hao, J.; Zhang, Q.; Wang, Y.; Zhu, Y. Role of Bcl 2 on drug resistance in breast cancer polyploidy induced spindle poisons. Oncol. Lett., 2020, 19(3), 1701-1710.
[http://dx.doi.org/10.3892/ol.2020.11256] [PMID: 32194662]
[76]
Ploumaki, I.; Triantafyllou, E.; Koumprentziotis, I.A.; Karampinos, K.; Drougkas, K.; Karavolias, I.; Trontzas, I.; Kotteas, E.A. Bcl-2 pathway inhibition in solid tumors: a review of clinical trials. Clin. Transl. Oncol., 2023, 25(6), 1554-1578.
[http://dx.doi.org/10.1007/s12094-022-03070-9] [PMID: 36639602]
[77]
Wolf, P. BH3 mimetics for the treatment of prostate cancer. Front. Pharmacol., 2017, 8, 557.
[http://dx.doi.org/10.3389/fphar.2017.00557]
[78]
Espona-Fiedler, M.; Manuel-Manresa, P.; Benítez-García, C.; Fontova, P.; Quesada, R.; Soto-Cerrato, V.; Pérez-Tomás, R. Antimetastatic properties of prodigiosin and the BH3-mimetic obatoclax (GX15-070) in melanoma. Pharmaceutics, 2022, 15(1), 97.
[http://dx.doi.org/10.3390/pharmaceutics15010097] [PMID: 36678726]
[79]
Lima, K.; Vicari, H.P.; Carlos, J.A.E.G.; da Silva, J.C.L.; Figueiredo-Pontes, L.L.; Rego, E.M.; Machado-Neto, J.A. Obatoclax reduces cell viability of acute myeloid leukemia cell lines independently of their sensitivity to venetoclax. Hematol. Transfus. Cell Ther., 2022, 44(1), 124-127.
[http://dx.doi.org/10.1016/j.htct.2021.01.004] [PMID: 33753045]
[80]
Gao, F.; Lan, H.; Jiao, L.; Zuo, T.; Sun, N.; Hu, Z.; Huang, J. Inhibitory effect of obatoclax mesylate-Loaded nanoparticles on lung cancer through Bcl-2 pathway. Mater. Express, 2023, 13(2), 283-289.
[http://dx.doi.org/10.1166/mex.2023.2344]
[81]
Daïri, K.; Yao, Y.; Faley, M.; Tripathy, S.; Rioux, E.; Billot, X.; Rabouin, D.; Gonzalez, G.; Lavallée, J-F.; Attardo, G. A scalable process for the synthesis of the bcl inhibitor obatoclax. Org. Process Res. Dev., 2007, 11(6), 1051-1054.
[http://dx.doi.org/10.1021/op7001613]
[82]
Maji, S. Chapter three - Bcl-2 antiapoptotic family proteins and chemoresistance in cancer.In: Advances in Cancer Research; Tew, K.D.; Fisher, P.B., Eds.; Academic Press, 2018, Vol. 137, pp. 37-75.
[http://dx.doi.org/10.1016/bs.acr.2017.11.001]
[83]
Lin, S.R.; Chen, Y.H.; Tseng, F.J.; Weng, C.F. The production and bioactivity of prodigiosin: quo vadis? Drug Discov. Today, 2020, 25(5), 828-836.
[http://dx.doi.org/10.1016/j.drudis.2020.03.017] [PMID: 32251776]
[84]
Soto-Cerrato, V.; Viñals, F.; Lambert, J.R.; Pérez-Tomás, R. The anticancer agent prodigiosin induces p21WAF1/CIP1 expression via transforming growth factor-beta receptor pathway. Biochem. Pharmacol., 2007, 74(9), 1340-1349.
[http://dx.doi.org/10.1016/j.bcp.2007.07.016] [PMID: 17765876]
[85]
Yenkejeh, R.A.; Sam, M.R.; Esmaeillou, M. Targeting survivin with prodigiosin isolated from cell wall of Serratia marcescens induces apoptosis in hepatocellular carcinoma cells. Hum. Exp. Toxicol., 2017, 36(4), 402-411.
[http://dx.doi.org/10.1177/0960327116651122] [PMID: 27334973]
[86]
Zhu, Z. Unveiling the anticancer mechanisms of prodigiosin by inhibiting of CDK1, TOP2A, and AURKB expression in cervical carcinoma. [Epub ahead of Print]. 2024.
[http://dx.doi.org/10.21203/rs.3.rs-3829039/v1]
[87]
Hong, B.; Prabhu, V.V.; Zhang, S.; van den Heuvel, A.P.J.; Dicker, D.T.; Kopelovich, L.; El-Deiry, W.S. Prodigiosin rescues deficient p53 signaling and antitumor effects via upregulating p73 and disrupting its interaction with mutant p53. Cancer Res., 2014, 74(4), 1153-1165.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0955] [PMID: 24247721]
[88]
Yamamoto, C.; Takemoto, H.; Kuno, K.; Yamamoto, D.; Nakai, K.; Baden, T.; Kamata, K.; Hirata, H.; Watanabe, T.; Inoue, K. Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human colon cancer cell lines in vitro. Oncol. Rep., 2001, 8(4), 821-824.
[http://dx.doi.org/10.3892/or.8.4.821] [PMID: 11410791]
[89]
Branco, P.C.; Pontes, C.A.; Rezende-Teixeira, P.; Amengual-Rigo, P.; Alves-Fernandes, D.K.; Maria-Engler, S.S.; da Silva, A.B.; Pessoa, O.D.L.; Jimenez, P.C.; Mollasalehi, N.; Chapman, E.; Guallar, V.; Machado-Neto, J.A.; Costa-Lotufo, L.V. Survivin modulation in the antimelanoma activity of prodiginines. Eur. J. Pharmacol., 2020, 888, 173465.
[http://dx.doi.org/10.1016/j.ejphar.2020.173465] [PMID: 32814079]
[90]
Matarlo, J.S.; Krumpe, L.R.H.; Heinz, W.F.; Oh, D.; Shenoy, S.R.; Thomas, C.L.; Goncharova, E.I.; Lockett, S.J.; O’Keefe, B.R. The natural product butylcycloheptyl prodiginine binds pre-miR-21, inhibits Dicer-mediated processing of pre-miR-21, and blocks cellular proliferation. Cell Chem. Biol., 2019, 26(8), 1133-1142.e4.
[http://dx.doi.org/10.1016/j.chembiol.2019.04.011] [PMID: 31155509]
[91]
Li, J.; Xu, J.; Li, Z. Obatoclax, the pan-Bcl-2 inhibitor sensitizes hepatocellular carcinoma cells to promote the anti-tumor efficacy in combination with immune checkpoint blockade. Transl. Oncol., 2021, 14(8), 101116.
[http://dx.doi.org/10.1016/j.tranon.2021.101116] [PMID: 33975180]
[92]
Abrahantes-Pérez, M.C.; Reyes-González, J.; Véliz Ríos, G.; Bequet-Romero, M.; Gómez Riera, R.; Anais Gasmury, C.; Huerta, V.; González, L.J.; Canino, C.; Garcia, J.; Váldez, J.; Reyes, B.; Váldes, R.; Martínez, E. Cytotoxic proteins combined with prodigiosin obtained from Serratia marcescens have both broad and selective cytotoxic activity on tumor cells. In: J. Chemother., 2006, 18(2), 172-181.
[http://dx.doi.org/10.1179/joc.2006.18.2.172] [PMID: 16736886]
[93]
Berning, L.; Schlütermann, D.; Friedrich, A.; Berleth, N.; Sun, Y.; Wu, W.; Mendiburo, M.J.; Deitersen, J.; Brass, H.U.C.; Skowron, M.A.; Hoffmann, M.J.; Niegisch, G.; Pietruszka, J.; Stork, B. Prodigiosin sensitizes sensitive and resistant urothelial carcinoma cells to cisplatin treatment. Molecules, 2021, 26(5), 1294.
[http://dx.doi.org/10.3390/molecules26051294] [PMID: 33673611]
[94]
Brown, J.R.; Tesar, B.; Yu, L.; Werner, L.; Takebe, N.; Mikler, E.; Reynolds, H.M.; Thompson, C.; Fisher, D.C.; Neuberg, D.; Freedman, A.S. Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia. Leuk. Lymphoma, 2015, 56(12), 3336-3342.
[http://dx.doi.org/10.3109/10428194.2015.1048441] [PMID: 25971907]
[95]
Chiappori, A.A.; Schreeder, M.T.; Moezi, M.M.; Stephenson, J.J.; Blakely, J.; Salgia, R.; Chu, Q.S.; Ross, H.J.; Subramaniam, D.S.; Schnyder, J.; Berger, M.S. A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer. Br. J. Cancer, 2012, 106(5), 839-845.
[http://dx.doi.org/10.1038/bjc.2012.21] [PMID: 22333598]
[96]
Chiappori, A.; Williams, C.; Northfelt, D.W.; Adams, J.W.; Malik, S.; Edelman, M.J.; Rosen, P.; Van Echo, D.A.; Berger, M.S.; Haura, E.B. Obatoclax mesylate, a pan-bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer. J. Thorac. Oncol., 2014, 9(1), 121-125.
[http://dx.doi.org/10.1097/JTO.0000000000000027] [PMID: 24346101]
[97]
Paik, P.K.; Rudin, C.M.; Brown, A.; Rizvi, N.A.; Takebe, N.; Travis, W.; James, L.; Ginsberg, M.S.; Juergens, R.; Markus, S.; Tyson, L.; Subzwari, S.; Kris, M.G.; Krug, L.M. A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies. Cancer Chemother. Pharmacol., 2010, 66(6), 1079-1085.
[http://dx.doi.org/10.1007/s00280-010-1265-5] [PMID: 20165849]
[98]
Paik, P.K.; Rudin, C.M.; Pietanza, M.C.; Brown, A.; Rizvi, N.A.; Takebe, N.; Travis, W.; James, L.; Ginsberg, M.S.; Juergens, R.; Markus, S.; Tyson, L.; Subzwari, S.; Kris, M.G.; Krug, L.M. A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer. Lung Cancer, 2011, 74(3), 481-485.
[http://dx.doi.org/10.1016/j.lungcan.2011.05.005] [PMID: 21620511]
[99]
Tunca Koyun, M.; Sirin, S.; Aslim, B.; Taner, G.; Nigdelioglu Dolanbay, S. Characterization of prodigiosin pigment by Serratia marcescens and the evaluation of its bioactivities. Toxicol. In Vitro, 2022, 82, 105368.
[http://dx.doi.org/10.1016/j.tiv.2022.105368] [PMID: 35476923]
[100]
Guryanov, I.; Naumenko, E.; Akhatova, F.; Lazzara, G.; Cavallaro, G.; Nigamatzyanova, L.; Fakhrullin, R. Selective cytotoxic activity of prodigiosin@halloysite nanoformulation. Front. Bioeng. Biotechnol., 2020, 8, 424.
[http://dx.doi.org/10.3389/fbioe.2020.00424] [PMID: 32528938]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy