Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Wawruszak, Anna; Łuszczki, Jarogniew J.; Hałasa, Marta; Okon, Estera; Landor, Sebastian K.-J.; Sahlgren, Cecilia; Rivero-Müller, Adolfo; Stepulak, Andrzej

doi:10.3390/ijms22105184

Cited by 7 publications

(9 citation statements)

References 40 publications

(75 reference statements)

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“…Suberoylanilide hydroxamic acid (vorinostat, SAHA; C 14 H 20 N 2 O 3 ) is the first generation HDAC pan-inhibitor belonging to the hydroxamic acids group of HDIs approved by FDA [ 68 , 92 , 93 ]. The HDAC catalytic activity inhibition by SAHA is based on its binding to the zinc ion located in the enzyme catalytic domain [ 58 , 94 ].…”

Section: Saha and Breast Cancermentioning

confidence: 99%

“…Therefore, attempts are made to test the effects of SAHA in polytherapy [ 108 , 114 ]. There are many in vitro and in vivo studies showing the efficacy of combining SAHA with other active compounds that are currently available in the treatment of different types of cancer [ 92 , 108 , 114 , 115 ].…”

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

“…All these findings suggest that SAHA could be combined with CDDP to optimize treatment regimens in different types of BC [ 108 ]. The influence of the Notch1 activity on the pharmacological interaction between CDDP and SAHA was also determined in MCF7 luminal [ 92 ] and TNBC cells [ 115 ]. MCF7 and MDA-MB-231 BC cells were genetically modified in order to express a differential level of Notch1 activity.…”

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

“…The combination of CDDP with SAHA in MDA-MB-231 TNBC cells with increased activity of Notch1 yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP with SAHA in MDA-MB-231 TNBC cells with decreased activity of Notch1. All these studies suggest that SAHA might be considered as a potential therapeutic agent in combination with CDDP against Notch1-altered luminal as well as some types of TNBC with altered Notch1 activity ( Table 3 ) [ 92 , 115 ].…”

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

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Vorinostat (SAHA) and Breast Cancer: An Overview

Wawruszak

Borkiewicz

Okon

et al. 2021

Cancers

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Vorinostat (SAHA), an inhibitor of class I and II of histone deacetylases, is the first histone deacetylase inhibitor (HDI) approved for the treatment of cutaneous T-cell lymphoma in 2006. HDIs are promising anticancer agents that inhibit the proliferation of many types of cancer cells including breast carcinoma (BC). BC is a heterogeneous disease with variable biological behavior, morphological features, and response to therapy. Although significant progress in the treatment of BC has been made, high toxicity to normal cells, serious side effects, and the occurrence of multi-drug resistance limit the effective therapy of BC patients. Therefore, new active agents which improve the effectiveness of currently used regimens are highly needed. This manuscript analyzes preclinical and clinical trials data of SAHA, applied individually or in combination with other anticancer agents, considering different histological subtypes of BC.

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Section: Saha and Breast Cancermentioning

confidence: 99%

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

Section: “Saha Et Al” and Breast Cancermentioning

confidence: 99%

See 2 more Smart Citations

Vorinostat (SAHA) and Breast Cancer: An Overview

Wawruszak

Borkiewicz

Okon

et al. 2021

Cancers

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“…BC is a very diversified disease with alternating morphological features, behavior, and response to anticancer therapy [ 4 , 5 , 6 ]. There are five main molecular subtypes of BC based on the inherency of the estrogen (ER) [ 4 ], progesterone (PR) [ 7 ] and human epidermal growth factor (HER2) [ 8 ] receptors, as well as the intensity of proliferation index-67 (Ki-67) [ 9 ], including luminal A (ER+/PR+; HER2−; Ki67−) [ 10 ], luminal B ((ER+/PR+; HER2−; Ki67+)/(ER+/PR+; HER2+; Ki67+)) [ 11 ], HER2-overexpressed (ER−/PR−; HER2+) [ 12 ], triple-negative breast cancer (TNBC) (ER−/PR−; HER2−) [ 13 ] and normal-like BC (ER+/PR+; HER2−; Ki67−) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Pharmacological Interactions between SIRT2 Inhibitor AGK2 and Paclitaxel in Different Molecular Subtypes of Breast Cancer Cells

Wawruszak

Łuszczki

Czerwonka

et al. 2022

Cells

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Breast carcinoma (BC) is the most commonly diagnosed type of cancer in women in the world. Although the advances in the treatment of BC patients are significant, numerous side effects, severe toxicity towards normal cells as well as the multidrug resistance (MDR) phenomenon restrict the effectiveness of the therapies used. Therefore, new active compounds which decrease the MDR, extend disease-free survival, thereby ameliorating the effectiveness of the current treatment regimens, are greatly needed. Histone deacetylase inhibitors (HDIs), including sirtuin inhibitors (SIRTi), are the epigenetic antitumor agents which induce a cytotoxic effect in different types of cancer cells, including BC cells. Currently, combined forms of therapy with two or even more chemotherapeutics are promising antineoplastic tools to obtain a better response to therapy and limit adverse effects. Thus, on the one hand, much more effective chemotherapeutics, e.g., sirtuin inhibitors (SIRTi), are in demand; on the other hand, combinations of accepted cytostatics are trialed. Thus, the aim of our research was to examine the combination effects of a renowned cytotoxic drug paclitaxel (PAX) and SIRT2 inhibitor AGK2 on the proliferation and viability of the T47D, MCF7, MDA-MB-231, MDA-MB-468, BT-549 and HCC1937 BC cells. Moreover, cell cycle arrest and apoptosis induction were explored. The type of pharmacological interactions between AGK2 and PAX in different molecular subtypes of BC cells was assessed using the advanced isobolographic method. Our findings demonstrated that the tested active agents singly inhibited viability and proliferation of BC cells as well as induced cell cycle arrest and apoptosis in the cell-dependent context. Additionally, AGK2 increased the antitumor effect of PAX in most BC cell lines. We observed that, depending on the BC cell lines, the combinations of tested drugs showed synergistic, additive or antagonistic pharmacological interaction. In conclusion, our studies demonstrated that the consolidated therapy with the use of AGK2 and PAX can be considered as a potential therapeutic regimen in the personalized cure of BC patients in the future.

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Additive pharmacological interaction between sirtuin inhibitor cambinol and paclitaxel in MCF7 luminal and MDA-MB-231 triple-negative breast cancer cells

et al. 2022

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Background Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in women worldwide. Sirtuin inhibitors (SIRTi), belonging to the histone deacetylase inhibitors group (HDIs), are potent epigenetic drugs that have been investigated for therapeutic use in different clinical disorders, including hematological malignancies and solid tumors. Methods The influence of cambinol (CAM; SIRTi) used individually or in combination with standard chemotherapeutic paclitaxel (PAX) on viability (MTT assay), proliferation (BrdU assay), induction of apoptosis and cell cycle arrest (FACS analysis) was determined in MCF7 luminal and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The types of pharmacological drug–drug interaction between CAM and PAX were determined by an exact and rigorous pharmacodynamic method—an isobolography, to determine the presence of synergism, addition or antagonism between analyzed drugs using a variety of fixed-dose ratios. Results The combination of CAM and PAX at a fixed ratio of 1:1 exerted additive interaction in the viability of MCF7 and MDA-MB-231 BC cells. Both active agents used separately reduced viability and proliferation of BC cells as well as induced apoptosis and cell cycle arrest. These effects were much more evident in MCF7 than in MDA-MB-231 BC cells. Additionally, CAM combined with PAX increased anti-cancer activity compared to PAX used alone. Conclusion CAM might be considered a potential therapeutic agent individually or in combined therapy with PAX against luminal or TNBC. Graphical abstract

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Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Cited by 7 publications

References 40 publications

Vorinostat (SAHA) and Breast Cancer: An Overview

Vorinostat (SAHA) and Breast Cancer: An Overview

Assessment of Pharmacological Interactions between SIRT2 Inhibitor AGK2 and Paclitaxel in Different Molecular Subtypes of Breast Cancer Cells

Additive pharmacological interaction between sirtuin inhibitor cambinol and paclitaxel in MCF7 luminal and MDA-MB-231 triple-negative breast cancer cells

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