Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy

Thakur, Ajay D.; Joshi, Nitin; Shanmugam, Thanigaivel; Banerjee, Rinti

doi:10.1016/j.canlet.2012.08.022

Cited by 22 publications

(10 citation statements)

References 42 publications

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“…Nevertheless, despite not achieving the primary objectives related to significant increases in progression-free survival rates, some optimism still remained for this agent in advanced soft tissue sarcoma patients (Bailey, et al, 2006), as well as to warrant further evaluation of perifosine in combination with rituximab or other active agents in patients with relapsed/refractory Waldenstrom's macroglobulinemia (Ghobrial, et al, 2010), and with currently available therapies in renal cancer (Cho, et al, 2012). Furthermore, a number of studies have reported the potentiation of antitumor activity following combination of perifosine with distinct anticancer drugs in cancer cells derived from several types of leukemia (Nyakern, et al, 2006;Papa, et al, 2008;Tazzari, et al, 2008), multiple myeloma Hideshima, et al, 2006), osteosarcoma (Yao, et al, 2013), medulloblastoma (Kumar, et al, 2009), lung cancer (Elrod, et al, 2007), colon cancer (M. B. Chen, et al, 2012, and glioma (Momota, et al, 2005), as well as following combination of miltefosine with different anticancer compounds or treatments in distinct cancer cell types (Haberkorn, et al, 1992;Papagiannaros, et al, 2006;Spruss, et al, 1993;Thakur, et al, 2013). Thus, phase II clinical trials were conducted with…”

Section: Alkylphosphocholinesmentioning

confidence: 99%

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed.

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Section: Alkylphosphocholinesmentioning

confidence: 99%

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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“…2,3,9,10 However, the use of nanocarriers as drug delivery systems for chemotherapeutic agents may be an alternative to decrease the chance of unanticipated adverse effects and maximize the therapeutic effects of encapsulated drugs. 11 Recently, the use of liposome-encapsulated paclitaxel and miltefosine provided synergistic effect on human glioblastoma cells resistant to chemotherapeutic agents, with a sustained release of these drugs and reversal of resistance. 11 Cationic lipids are amphiphilic molecules that have been used as a delivery system for nucleic acid and have several advantages, such as the fact that these liposomes are endogenous and biodegradable after administration.…”

mentioning

confidence: 99%

“…11 Recently, the use of liposome-encapsulated paclitaxel and miltefosine provided synergistic effect on human glioblastoma cells resistant to chemotherapeutic agents, with a sustained release of these drugs and reversal of resistance. 11 Cationic lipids are amphiphilic molecules that have been used as a delivery system for nucleic acid and have several advantages, such as the fact that these liposomes are endogenous and biodegradable after administration. [12][13][14][15] This is beneficial because the presence of endogenous enzymes can break down the lipid components of the liposomes.…”

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confidence: 99%

Potential antitumor activity of novel DODAC/PHO-S liposomes

Luna

Saraiva²,

Filho³

et al. 2016

IJN

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In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ∼50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC 50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC 50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G 2 /M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and apoptotic bodies after DODAC/PHO-S treatment. Cationic liposomal formulation for PHO-S delivery promoted cytotoxicity more selectively and effectively against B16F10 and Hepa1c1c7 cells. Thus, the DODAC/PHO-S liposomal formulation presents great potential for preclinical studies.

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“…Lipossomas encapsulando placlitaxel e mitelfosina propiciaram um efeito sinérgico em células de glioblastoma humano resistentes à quimioterapia, havendo uma liberação sustentada dos fármacos e favorecendo a reversão da resistência destas células àqueles agentes (Thakur et al, 2013). Os sistemas de nanocarreadores revolucionaram as estratégias para a liberação de fármacos e representam um importante impacto no desenvolvimento de agentes anticâncer mais seletivos e efetivos (Kumar et al, 2012;Mattheolabakis et al, 2012;Urbinati et al, 2012;Drbohlavova et al, 2013;Pandey et al, 2016).…”

Section: Discussionunclassified

Potencial antitumoral da formulação lipossomal DODAC/fosfoetanolamina sintética no modelo de hepatocarcinoma

Luna¹

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chegar a este momento. Entre as alternâncias de tempestades e dias ensolarados, no mar bravio que é a vida, sempre fostes o meu farol ao norte e, também, os ventos que sopram nas velas da minha embarcação, impulsionando-me.Aos meu pais, Marcos Lima e Norma Luna, por todo incentivo e encorajamento.Agradeço pelos valores e ensinamentos que recebi, aos quais sempre buscarei ser fiel.Aos meus irmãos, Tamires Luna e Lucas Luna, por serem um dos alicerces da minha existência. Em momento de felicidade, vocês compartilharam comigo os sorrisos mais sinceros e a euforia da alegria; nos dias tristes, acalentaram minha alma com palavras brandas e sábias; nas dificuldades, me encorajaram para eu dar o meu melhor e, simplesmente, descansar em Deus. Caminhando percorremos o caminho em direção à "utopia"; sim ela se afastou, eu sei, mas juntos chegamos até aqui e em companhia continuaremos a caminhar.Ao meu tio e sua esposa, Assis Luna e Sueli Luna, pelo apoio concedido para que eu pudesse me estabelecer em São Paulo. Vocês tornaram viável este momento.A Alethéia Lacerda, minha esposa, companheira e amiga. Utilizando as palavras do grande poeta Vinícius de Moraes: "A vida é arte do encontro, embora haja tanto desencontro pela vida". Fui agraciado por ter encontrado você, que inusitadamente veio "escondida" entre os papers, experimentos e pipetas. Você me fez redescobrir o significado da palavra compartilhar, trazendo "novos" sentimentos e momentos para minha existência. Obrigado por todo amor e auxílio, que tantas vezes me trouxeram alento e completude, me trazendo a certeza de que a felicidade só é plena quando partilhada. TE AMO! Ao Dr. Durvanei Augusto Maria, pelas oportunidades, ensinamentos valiosos, confiança e amizade. Agradeço por todo empenho e dedicação com os quais o senhor orientou este trabalho, estando sempre disposto e acessível para ajudar. Obrigado por me receber em seu laboratório e pelo acolhimento.A Dra. Elia Tamaso Espin Garcia Caldini, pela amizade e palavras de incentivo. A Senhora é inspiradora e me faz enxergar a vida acadêmica de uma maneira mais ampla e nobre.A Dra. Marcia Saldanha Kubrusly, por abrir as portas do seu laboratório, possibilitando as análises moleculares deste estudo. Além disto, e mais importante que isto, obrigado pela amizade, ensinamentos, apoio e conversas descontraídas, que sempre trouxeram ao meu rosto um doce e verdadeiro sorriso.A Dra. Juliana Pereira, pelas grandes contribuições para este trabalho. Obrigado por viabilizar as análises de citometria, permitindo a utilização dos equipamentos disponíveis em seu laboratório.A Dra. Greice Kelle Viegas Saraiva, pelo auxílio na preparação dos lipossomas e ensaios bioquímicos.A todos os Professores membros da banca do exame de qualificação, obrigado por todas as sugestões e contribuições. "Apesar das ruínas e da morte, Onde sempre acabou cada ilusão, A força dos meus sonhos é tão forte, Que de tudo renasce a exaltação E nunca as minhas mãos ficam vazias". Sophia de Mello Breyner Andresen"É melhor tentar e falhar, que preocupar-se e ver...

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Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy

Cited by 22 publications

References 42 publications

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Potential antitumor activity of novel DODAC/PHO-S liposomes

Potencial antitumoral da formulação lipossomal DODAC/fosfoetanolamina sintética no modelo de hepatocarcinoma

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