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Colchicine and paclitaxel are two common drugs used in chemotherapy to halt tumor growth. In the present study IAR 20 cells were treated for 24 and 48 hr with colchicine and paclitaxel alone, in combination or no drug which served as a control. Through the use of Western blotting, we determined that the treatments affected expression due of several proteins including bcl-2, bax, p53 and caspase-8. The changes observed in protein expression due to the treatments correlated to the photomicrographs of the cells in culture and cell viability, indicating that the drugs were activating and initiating apoptosis. Interestingly, morphological changes such as membrane blebbing and cell swelling (indicators of apoptosis) were observed in the treated cultures and even more important the combined treatment yielded both changes in morphology. Also, activity assays were performed to study the effects the treatments had on the activities of SAPK/JNK and caspase-3, known activators of apoptosis. High activities of SAPK/JNK and caspase-3 in 48 hr treatments directly influenced cell viability in that the treatments with the highest activities yielded the lowest cell numbers, indicating that apoptosis was occurring. Based on these findings it was concluded that combined treatments of colchicine and paclitaxel are not advantageous in hepatocytes and could provide some insight into the treatment of liver cancer. Additionally, it appeared the drugs were initiating apoptosis in a p53 independent manner. / Department of Biology

This paper presents the fabrication of controlled release devices for anticancer drug paclitaxel using supercritical antisolvent method. The thermodynamic and hydrodynamic effects during supercritical antisolvent process on the particle properties obtained were investigated. Scanning electron microscopy was employed to study particle sizes and morphologies achieved. It was observed that increasing supercritical pressure improves the surface morphology of particles obtained, and increasing the flow rate of the organic solution jet reduces the particle sizes obtained. A modified Supercritical Antisolvent with Enhanced Mass transfer setup was developed to produce monodispersed nanoparticles with high recovery yield. High performance liquid chromatography was used to determine the encapsulation efficiency and in vitro release profiles of paclitaxel loaded particles obtained. The encapsulation efficiencies of particles obtained using the modified SASEM process were high and up to 83.5%, and sustained release of paclitaxel from the polymer matrix was observed over 36 days release. The thermogram properties of the particles were also analyzed using differential scanning calorimetry to determine the crystalline state of polymer and drug. / Singapore-MIT Alliance (SMA)

Submitted by Nivaldo Melo (nivaldo.melo@ufvjm.edu.br) on 2015-11-30T16:45:15Z No. of bitstreams: 2 marcos_vinicius_barbosa.pdf: 2721412 bytes, checksum: 173504d75a25f2de0569ca85af50f0df (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-12-03T16:06:21Z (GMT) No. of bitstreams: 2 marcos_vinicius_barbosa.pdf: 2721412 bytes, checksum: 173504d75a25f2de0569ca85af50f0df (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) / Made available in DSpace on 2015-12-03T16:06:22Z (GMT). No. of bitstreams: 2 marcos_vinicius_barbosa.pdf: 2721412 bytes, checksum: 173504d75a25f2de0569ca85af50f0df (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Previous issue date: 2014 / Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG) / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Rede Mineira de Pesquisas em Nanobiotecnologia (Nanobiomg) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Capes) / O paclitaxel (PTX) ? um agente quimioter?pico usado no tratamento de v?rios tipos de tumores s?lidos como c?ncer de pr?stata, mama e ov?rio. Devido a sua baixa solubilidade aquosa, o PTX (Taxol?) ? formulado em um ve?culo constitu?do por Cremophor EL? e ?lcool desidratado. No entanto, rea??es de hipersensibilidade aguda, nefrotoxicidade e neurotoxicidade, al?m de problemas de instabilidade f?sico-qu?mica t?m sido relatados com o uso do Taxol?. Diante disso, o objetivo desse estudo foi desenvolver um novo sistema lipossomal multifuncionalizado para veicular o PTX e avaliar a citotoxicidade em linhagens tumorais de c?ncer de mama (MCF-7 e MDA-MB-231). Inicialmente foi desenvolvido e validado um m?todo anal?tico para quantifica??o do PTX por espectrofotometria derivada no ultravioleta. O m?todo apresentou linearidade adequada e permitiu a quantifica??o do PTX na formula??o com adequada precis?o, exatid?o e especificidade. As formula??es propostas foram compostas por dioleilfosfatidiletanolamina (DOPE), hemisuccinato de colesterila (CHEMS), e diestearoilfosfatidiletanolamina associado ao polietilenoglicol 2000 (DSPE-PEG2000); ou por fosfatidilcolina de soja (SPC), DOPE, CHEMS e DSPE-PEG e preparadas pelo m?todo de hidrata??o do filme lip?dico. A influ?ncia da composi??o lip?dica qualitativa e quantitativa (10 e 20 mM) e da concentra??o do PTX (0,5; 1,0 ou 20 mg/mL) nas caracter?sticas f?sico-qu?micas dos lipossomas foi avaliada. Uma redu??o no teor de encapsula??o foi verificada na formula??o composta por DOPE:CHEMS:DSPE-PEG a medida que a concentra??o de PTX foi aumentada (p<0,05), rela??o que n?o foi observada para a formula??o com SPC. A associa??o com o PTX promoveu aumento significativo no di?metro m?dio das ves?culas em compara??o com a formula??o sem PTX e o aumento na concentra??o do f?rmaco tamb?m levou a um aumento no di?metro. O potencial zeta de todas as formula??es apresentou valores pr?ximos da neutralidade. Essa prepara??o apresentou boa estabilidade, com manuten??o do di?metro m?dio, teor de encapsula??o e potencial zeta durante 100 dias de armazenamento. Modifica??es da organiza??o supramolecular da DOPE indicativas de mudan?as de fase lamelar para n?o-lamelar em fun??o da redu??o do pH foram observadas nas prepara??es compostas por DOPE:CHEMS:DSPE-PEG. A inclus?o da SPC na bicamada, alterou a pH-sensibilidade do sistema e maior reten??o do PTX foi observada em pH mais ?cido quando comparada ? formula??o sem a SPC (p<0,05). A an?lise morfol?gica demonstrou a exist?ncia de part?culas esf?ricas regulares com di?metros heterog?neos para as formula??es contendo ou n?o PTX. A atividade citot?xica in vitro mostrou que o PTX associado aos lipossomas com folato (LpHSF-PTX) foi mais ativo que o PTX encapsulado nos lipossomas sem associa??o ao folato (LpHS-PTX) e que o PTX livre. Em suma, esses resultados sugerem que os LpHSF-PTX representam uma alternativa promissora para entrega intracelular do PTX no tratamento do c?ncer de mama. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2014. / ABSTRACT Paclitaxel (PTX) is a chemotherapeutic agent used in the treatment against various solid tumors such as prostate cancer, breast and epithelial ovarian carcinoma. Due to its low aqueous solubility, PTX is prepared in a vehicle composed of Cremophor EL? and dehydrated ethanol (Taxol?). However, acute hypersensitivity reactions, nephrotoxicity and neurotoxicity, as well as problems of physical-chemical instability have been reported with use of Taxol?. Thus, the purpose of this study was to develop a multifunctional liposomal system to carrier PTX, and to evaluate its cytotoxicity in tumor cell lines breast cancer (MCF-7 and MDA-MB-231). Firstly, an analytical method for quantification of PTX by derivative ultraviolet spectrophotometry was developed and validated. The method showed adequate linearity and allowed the quantification of PTX formulation with adequate precision, accuracy and sensitivity. The proposed formulations were composed by dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS) and distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG) or soy phosphatidylcholine (SPC), DOPE, CHEMS and DSPE-PEG and prepared by lipid film hydration method. The influence of the qualitative and quantitative lipid composition (10 and 20mM), and the PTX concentration (0.5, 1.0 and 2.0 mg/mL) on the physicochemical characteristics of liposomes was evaluated. A decrease in the encapsulation percentage was observed in formulation composed DOPE:CHEMS:DSPE-PEG as the PTX concentration was increased (p<0,05), however, this relation was not observed for formulations with SPC. The PTX association caused a significant increase in the mean diameter of the vesicle compared to the formulation without PTX and the increase in drug concentration also led to an increase in mean diameter. The zeta potential for all formulations showed values near neutrality. This preparation showed good stability, maintaining the average diameter, encapsulating percentage and zeta potential over 100 days of storage. Alterations in the supramolecular organization of DOPE indicative of changes in lamellar to non-lamellar phase due to pH reduction in formulation made up DOPE:CHEMS:DSPE-PEG could be observed. The inclusion of SPC in the bilayer decreased the pH sensitivity of this system and increased of PTX retention in more acidic pH was observed as compared to the formulation without SPC (p<0,05). Morphological analysis evidenced the existence of regular spherical vesicles with heterogeneous diameters in formulations with and without PTX. The in vitro cytotoxicity assay showed the PTX associated with liposomes folate-targeted (LpHSF-PTX) was more active in PTX encapsulated than in non-targeted liposomes (LpHS-PTX) and PTX free. These results suggest that the LpHSF-PTX represent a promising alternative for intracellular PTX delivery in the treatment of breast cancer.

Made available in DSpace on 2014-06-12T15:49:46Z (GMT). No. of bitstreams: 2 arquivo2023_1.pdf: 970359 bytes, checksum: 28503fe6b0401f09d8c88ae0157ca7f3 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A expansão das indicações para o uso dos stents farmacológicos, liberadores de sirolimus e de paclitaxel, inclui lesões de complexidade crescente e populações com perfil clínico diferente daquele dos estudos randomizados fundamentais. Os stents farmacológicos são altamente efetivos na redução das taxas de reestenose e da necessidade de revascularização da lesão-alvo, quando comparados aos stents convencionais. Estes resultados foram obtidos em pacientes estáveis, com lesões coronarianas pouco complexas, selecionados a partir de critérios rigorosos de inclusão e exclusão na rotina. Na prática clínica, tem-se expandido amplamente as indicações para o seu uso desde 2002, quando os stents farmacológicos tornaram-se disponíveis para uso clínico no Brasil. A introdução do stent farmacológico, com intuito de encontrar uma solução biológica e mecânica para minimizar a incidência de reestenose, conseguiu uma substancial diminuição na taxa desta reestenose, porém às custas de um risco maior de trombose tardia do stent. O presente artigo de revisão tem o objetivo de abordar as indicações e limitações ao uso dos stents farmacológicos, vez que existem questionamentos sobre a efetividade e a segurança tardias em situações de maior complexidade. Com esse objetivo, foram consultados artigos publicados em periódicos científicos e livros técnicos, coletados através do Google Acadêmico (http://www.scholar.google.com.br), Transcatheter Cardiovascular Therapeutics (http://www.tctmd.com) e do Pubmed (http://www.ncbi.nlm.nih.gov). Pretende-se analisar, em perspectiva, os riscos e benefícios dos stents farmacológicos com base nos dados disponíveis

Submitted by Gabriele Rodrigues (gabriele_r.valentim@hotmail.com) on 2016-09-02T15:40:29Z No. of bitstreams: 1 Dissertação - Francivaldo de Oliveira Lima Versiani.pdf: 3895432 bytes, checksum: de4557b6f975ae78826ce659e47f9f2f (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-13T12:53:07Z (GMT) No. of bitstreams: 1 Dissertação - Francivaldo de Oliveira Lima Versiani.pdf: 3895432 bytes, checksum: de4557b6f975ae78826ce659e47f9f2f (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-13T12:58:01Z (GMT) No. of bitstreams: 1 Dissertação - Francivaldo de Oliveira Lima Versiani.pdf: 3895432 bytes, checksum: de4557b6f975ae78826ce659e47f9f2f (MD5) / Made available in DSpace on 2016-09-13T12:58:01Z (GMT). No. of bitstreams: 1 Dissertação - Francivaldo de Oliveira Lima Versiani.pdf: 3895432 bytes, checksum: de4557b6f975ae78826ce659e47f9f2f (MD5) Previous issue date: 2011-08-30 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / O Paclitaxel é um agente quimioterápico muito utlizado no tratamento do câncer de mama e ovário, inclusive em estágios avançados. Devido sua hidrofobicidade, o Paclitaxel foi incorporado a uma nanoemulsão lipídica rica em colesterol (LDE) e teve um grupamento de ácido oléico associado à molécula primária, originando o oleato de Paclitaxel. Este trabalho teve a finalidade de avaliar a citotoxicidade e genotoxicidade do oleato de Paclitaxel incorporado à nanoemulsão lipídica rica em colesterol (LDE), comparando os resultados com o Paclitaxel comercial (Taxilan). Foram encontrados os seguintes resultados para o teste de hemólise em camundongos: LDE+OPTX: 59,04 μM (26,95-129,4); OPTX, TAX, OA, PTX : >100 μM; LDE: 58,26 μM (42,59-79,69). No teste de hemólise em eritrócitos humanos nenhuma substância causou hemólise, exceto o OA (94,2%). A citotoxicidade em ACP02 mostrou as CI50: LDE+OPTX: 17,65 μM (15,91-19,58); OPTX, PTX, OA: >100 μM; LDE: 51,75 μM (48,43-55,30). A citotoxicidade em MCF-7 mostrou as CI50: LDE+OPTX: 12,41 μM (9,38-16,41); OPTX, PTX, OA: >100 μM; LDE: 25,53 μM (21,23-30,70). A citotoxicidade em MDA-MB-231 mostrou as CI50: LDE+OPTX: 21,82 μM (19,20-24,80); OPTX, PTX, OA: >100 μM; LDE: 26,29 μM (24,17-28,59). A citotoxicidade em linfócitos humanos mostrou os seguintes resultados para CI50 em 24h: LDE+OPTX, LDE, OPTX, OA: >100 μM; TAX: 40,39 (28,23-57,78). Para 48h: OPTX, OA: >100 μM; TAX: 24,61 (15,61- 38,79); LDE: 47,20 μM (37,00-60,23); LDE+OPTX: 40,78μM (31,41-52,93); TAX: 24,61 μM. Para 72h: OPTX, OA: >100 μM; LDE: 39,06 μM; LDE+OPTX: 33,99 μM. O teste do Cometa mostrou que a nanoemulsão é genotóxica tanto em linfócitos quanto em células tumorais gástricas e de mama. No teste do Micronúcleo em 24 e 48 horas não houve aumento de frequência de micronúcleos em nenhuma substância. Portanto, verificou-se que a nanoemulsão rica em colesterol com oleato de Paclitaxel é citotóxica em células tumorais e em células normais, causando danos ao DNA de linfócitos e células de adenocarcinoma gástrico e de mama, somente nas maiores concentrações testadas (7,5 e 10 μM). / O Paclitaxel é um agente quimioterápico muito utlizado no tratamento do câncer de mama e ovário, inclusive em estágios avançados. Devido sua hidrofobicidade, o Paclitaxel foi incorporado a uma nanoemulsão lipídica rica em colesterol (LDE) e teve um grupamento de ácido oléico associado à molécula primária, originando o oleato de Paclitaxel. Este trabalho teve a finalidade de avaliar a citotoxicidade e genotoxicidade do oleato de Paclitaxel incorporado à nanoemulsão lipídica rica em colesterol (LDE), comparando os resultados com o Paclitaxel comercial (Taxilan). Foram encontrados os seguintes resultados para o teste de hemólise em camundongos: LDE+OPTX: 59,04 μM (26,95-129,4); OPTX, TAX, OA, PTX : >100 μM; LDE: 58,26 μM (42,59-79,69). No teste de hemólise em eritrócitos humanos nenhuma substância causou hemólise, exceto o OA (94,2%). A citotoxicidade em ACP02 mostrou as CI50: LDE+OPTX: 17,65 μM (15,91-19,58); OPTX, PTX, OA: >100 μM; LDE: 51,75 μM (48,43-55,30). A citotoxicidade em MCF-7 mostrou as CI50: LDE+OPTX: 12,41 μM (9,38-16,41); OPTX, PTX, OA: >100 μM; LDE: 25,53 μM (21,23-30,70). A citotoxicidade em MDA-MB-231 mostrou as CI50: LDE+OPTX: 21,82 μM (19,20-24,80); OPTX, PTX, OA: >100 μM; LDE: 26,29 μM (24,17-28,59). A citotoxicidade em linfócitos humanos mostrou os seguintes resultados para CI50 em 24h: LDE+OPTX, LDE, OPTX, OA: >100 μM; TAX: 40,39 (28,23-57,78). Para 48h: OPTX, OA: >100 μM; TAX: 24,61 (15,61- 38,79); LDE: 47,20 μM (37,00-60,23); LDE+OPTX: 40,78μM (31,41-52,93); TAX: 24,61 μM. Para 72h: OPTX, OA: >100 μM; LDE: 39,06 μM; LDE+OPTX: 33,99 μM. O teste do Cometa mostrou que a nanoemulsão é genotóxica tanto em linfócitos quanto em células tumorais gástricas e de mama. No teste do Micronúcleo em 24 e 48 horas não houve aumento de frequência de micronúcleos em nenhuma substância. Portanto, verificou-se que a nanoemulsão rica em colesterol com oleato de Paclitaxel é citotóxica em células tumorais e em células normais, causando danos ao DNA de linfócitos e células de adenocarcinoma gástrico e de mama, somente nas maiores concentrações testadas (7,5 e 10 μM).

Tumors evade immune system tumor-controlling functions. T cells critical to antitumor immunity are tolerogenic in tumor-burdened animals, and fail to lyse neoplastic cells. Our goal was to investigate the kinetics of immune dysfunction related to tumor-burdened host (TBH) memory T cell responses (or the lack thereof). We demonstrate tumor growth impairs T cell activation by modulating CD4+ T cell infiltration and systemic CD44 and CD62L activation marker expression, and by downregulating TBH TH1 cytokine production by splenic CD4+ T cells. Since chemotherapeutic treatments have potent cytostatic effects, we posited they enhance T cell dysfunctionality; which leads to limited therapeutic efficacy. Paclitaxel is a potent chemotherapeutic agent currently being administered in Stage III clinical trials; however, it reduces T cell proliferative capacity and interferon-γ (IFN-γ) production. In contrast, our data suggest that administration of low dose paclitaxel prolongs adaptive immunity in a limited capacity. We show paclitaxel enhances CD4highCD62Llow cell populations that drive TH1 cytokine production and prolongs the production of interleukin-2 (IL-2) in TBHs. We hypothesize that the initiation and maintenance of activated TH1 cell populations in patients during therapy serves as a reliable prognostic indicator of a favorable therapeutic response. Paclitaxel's limited therapeutic effects are due, in part, to its suppression of T cell activities; but the administration of low dose chemotherapy in combination with immunotherapeutic agents temporally takes advantage of paclitaxel's immunostimulatory capabilities. Our work will enhance current understanding of immune dysregulation during cancer development, and promote advances in the monitoring and development of combinatorial cancer treatments. / Master of Science

Human society has benefited greatly from plant secondary metabolites, often utilizing a variety of compounds as dyes, food additives, and drugs. In particular, pharmaceutical development has benefited greatly from plant secondary metabolites. One example of this utility is paclitaxel, a highly substituted diterpene approved in the treatment of breast cancer, ovarian cancer, non-small cell lung cancer, and the AIDSrelated Kaposi’s sarcoma. Demand of paclitaxel is likely to increase, due to the current examination of paclitaxel in numerous clinical trials against a variety of other cancers. Taxus cell culture represents a production source of paclitaxel to meet future demand. However, paclitaxel production through Taxus cell culture is often variable and low. Targeted metabolic engineering of Taxus to produce superior paclitaxelaccumulating lines is a viable strategy to address variable and low yields. To facilitate the production of genetically engineered Taxus cell lines, stable transformation is required to examine the long-term effect of gene expression in vitro. Additionally, suitable transient transformation systems are necessary to characterize novel Taxus genes related to paclitaxel accumulation. A transient particle bombardment-mediated transformation protocol was developed to introduce transgenes into Taxus cells in vitro. Additionally, agroinfiltration in Nicotiana benthamiana was examined as a system to express genes related to paclitaxel biosynthesis and lead to the accumulation of the first dedicated taxane, taxa- 4(5), 11(12)-diene. In regard to stable transformation, an Agrobacterium-mediated transformation protocol was developed, though this method requires further optimization for reliability and increased transformation efficiency. These transformation technologies will aid in the creation of elite paclitaxel-accumulating Taxus cell lines.

Titre de l'écran-titre (visionné le 17 avril 2023) / « Ce mémoire de maîtrise, présente l'étude de l'efficacité d'une nouvelle stratégie thérapeutique impliquant des inhibiteurs d'interface du complexe CRIF1-CDK2 (Facteur 1 Interagissant avec le CR6-Kinase Dépendante de la Cycline 2) pour contrer la résistance au taxol dans le traitement du cancer du sein triple négatif (CSTN). Le CSTN est un sous-type très agressif qui représente environ 15 % de tous les cancers du sein. Les options de traitement disponibles pour le CSTN sont limitées en raison de l'absence de trois récepteurs. La chimiothérapie demeure le pilier du traitement médical systémique pour le CSTN. Néanmoins, après quelques mois de traitement, 50% des patientes développent une résistance contre l'agent chimique utilisé: le taxol. Le présent projet s'adresse à cette catégorie des patientes. L'objectif principal de cette étude était donc de vérifier la capacité de deux inhibiteurs sélectifs de l'interface du complexe CRIF1-CDK2 : F1142-3225 et F0922-0913 à promouvoir l'action du taxol. Les sous-objectifs étaient de tester ces deux inhibiteurs pour : i) déterminer leur activité antiproliférative sur deux lignées CSTN : MDA-MB-231 et MDA-MB-468 et la lignée des cellules de sein normales : MCF-10A. Et de vérifier leur effet sur ii) le contrôle du cycle cellulaire, et iii) l'expression du CDK2 dans ces trois lignées. Nos principaux résultats ont montré que lorsqu'ils sont appliqués seuls ou combinés au taxol, ces deux inhibiteurs sélectifs ont réduit significativement la viabilité des cellules CSTN et ils ont modulé le cycle des cellules cancéreuses induisant des dommages irréparables dans ces dernières, les conduisant à l'apoptose, et ce sans affecter les cellules non-cancéreuses. Ils présentent donc des avantages de spécificité et de sélectivité en augmentant significativement la sensibilité des cellules cancéreuses à la chimiothérapie. Dans l'ensemble, ces inhibiteurs sélectifs peuvent servir de voie thérapeutique attrayante pour promouvoir la chimiosensibilité dans le cancer du sein triple négatif. » / « This master's thesis presents the study of the effectiveness of a new therapeutic strategy involving interface inhibitors of the CRIF1-CDK2 complex (Factor 1 Interacting with CR6-Cyclin Dependent Kinase 2) to counter resistance to taxol in the treatment of triple negative breast cancer (TNBC). TNBC is a very aggressive subtype that accounts for about 15% of all breast cancers. The available treatment options for TNBC are limited due to the absence of three receptors. Chemotherapy remains the mainstay of systemic medical treatment for TNBC. Nevertheless, after a few months of treatment, 50% of patients develop resistance against the chemical agent used: taxol. This project is aimed at this category of patients. The main objective of this study was to verify the ability of two selective CRIF1-CDK2 interface inhibitors: F1142-3225 and F0922-0913 to promote the action of taxol. The sub-objectives were to test these two inhibitors to: i) determine their antiproliferative activity on two CSTN cell-lines: MDA-MB-231 and MDA-MB-468, and the cell-line MCF-10A, representing normal breast cells. And to verify their effect on ii) the control of the cell cycle, and iii) the expression of CDK2 in these three cell-lines. Our main results showed that when applied alone or combined with taxol, these two selective inhibitors significantly reduced the viability of TNBC cells and they modulated the cell-cycle of cancerous cells inducing irreparable damage in the latter, leading them to apoptosis, without affecting non-cancerous cells. Therefore, they have advantages of specificity and selectivity by significantly increasing the sensitivity of cancer cells to chemotherapy. Taken together, these selective inhibitors may serve as an attractive therapeutic strategy to promote chemosensitivity in triple-negative breast cancer. »