Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

Hałasa, Marta; Łuszczki, Jarogniew J.; Dmoszyńska‐Graniczka, Magdalena; Baran, Marzena; Okon, Estera; Stepulak, Andrzej; Wawruszak, Anna

doi:10.3390/ijms22168573

Cited by 8 publications

(6 citation statements)

References 60 publications

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“…Antagonistic pharmacological CAM:PAX interaction we were confirmed in isobolographic analysis for BT-549 and MDA-MB-468 TNBC cells. Similar results were obtained in our previous study [ 35 ]. CAM and another chemotherapeutic-CDDP administered separately induced inhibition of cell viability in each analyzed BC cell line in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 93%

“…However, CAM in combination with CDDP significantly decreased cytotoxicity and the percentage of cells with active caspase-3 caused by these drugs used alone. An isobolographic analysis confirmed the antagonistic effect of CDDP and CAM in BC cell lines with different phenotypes: MCF7, T47D estrogen receptor-positive and MDA-MB-231, MDA-MB-468 TNBC cells [ 35 ]. Additionally, CAM in combination with doxorubicin did not show a significant synergetic effect in neuroblastoma cells; although, CAM applied individually was effective in DOX-sensitive cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Wawruszak

Łuszczki

Okon

et al. 2022

IJMS

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Breast cancer (BC) is a heterogeneous disease with different intrinsic subtypes. The most aggressive subtype of BC–triple-negative breast cancer (TNBC) is characterized by high heterogeneity and metastasis rate, poor prognosis and lack of therapeutic targets due to the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Targeted therapies have been approved for many other cancers and even other subtypes of BC, but treatment options for TNBC are still mainly limited to chemotherapy. Therefore, new, more effective treatment regimens are needed. Combined chemotherapy with two or more active agents is considered a promising anti-neoplasm tool in order to achieve better therapeutic response and reduce therapy-related adverse effects. The study demonstrated an antagonistic effect commonly used in TNBC therapy cytostatic drug-paclitaxel (PAX) and sirtuin inhibitor: cambinol (CAM) in BT-549, MDA-MB-468 and HCC1937 TNBC cell lines. The type of pharmacological interaction was determined by a precise and rigorous pharmacodynamic method-isobolographic analysis. The cytotoxic and anti-proliferative effects of CAM used alone or combined with PAX were determined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU) assays, respectively. Induction of apoptosis in TNBC cell lines after PAX and CAM treatment applied individually or in combination was determined by flow cytometry (FACS) as a number of cells with active caspase-3. It has been observed that both agents used separately inhibit cell proliferation and induce apoptosis; however, applying them in combination ameliorated antiproliferative and pro-apoptotic effects in all analyzed TNBC cell lines. Our results demonstrate that CAM and PAX used in combination act antagonistically, limiting anti-cancer efficacy and showing the importance of preclinical testing.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Wawruszak

Łuszczki

Okon

et al. 2022

IJMS

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“…No sirtuin inhibitors have been approved by FDA so far. Preclinical studies indicate that some sirtuin inhibitors show promising in vitro results used alone against solid tumors [ 83 , 84 , 85 , 86 , 87 ]; however, the data obtained from combined-treatment research are controversial, concluding different types of pharmacological interactions between tested drugs [ 88 , 89 , 90 , 91 ].…”

Section: Histone Deacetylase Inhibitors (Hdis)mentioning

confidence: 99%

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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“…Notably, silencing ONECUT2 or treating with CSRM617 both contributed to elevated sensitivity of chemotherapy. The combinations of 5-FU or cisplatin with oncogene inhibitors were already used to enhance the antitumor activity in types of cancers [24][25][26][27][28][29]. Thus, ONECUT2 inhibitor CSRM617 was supposed to elicit a signi cant strength on chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Upregulated ONECUT2 impeded the efficacy of 5-FU treatment to relapsed patients and might be an emerging indicator of chemotherapy in gastric cancer

Wang

Zhu

Chen

et al. 2022

Preprint

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Background Chemotherapeutic resistance is a main obstacle for prolonging the lifetime of gastric cancer (GC) patients, so new emerging solutions still remain to be investigated. We aim to identify an effective target, ONECTU2, for chemotherapy of GC patient, particularly relapsed patients.Methods STAD patients matched with clinical features and transcriptome sequencing data from TCGA were used in this study. Gene set enrichment analyses (GSEA) were performed using 100 patients who were divided average according to ONECUT2 level. Cytotoxic assays for 5-FU and cisplatin were used to test the role of chemotherapeutic resistance of ONECUT2 in GC cells. 30 relapsed patients with previously resected tumor samples were collected to validate the efficacy of ONECUT2 in GC chemotherapy.Results ONECUT2 was a crucial regulator of Disease-Free Interval (DFI) in GC patients with reoccurrence once having chemotherapeutic treatment. Gene set enrichment analysis (GSEA) results suggest that upregulated ONECUT2 is positively correlated with the increased ability of xenobiotic drug metabolism, which might contribute to the pharmaceutical resistance in GC. Targeting ONECUT2 reduced half-maximal inhibitory concentration (IC50) of 5-FU and cisplatin in GC cells. The efficacy of 5-FU treatment was negatively correlated with ONECUT2 mRNA level of tumor samples derived from GC patients who relapsed after surgical resection.Conclusions These findings indicate that ONECUT2 displays a drug-resistant function in GC, providing a new therapeutic target for GC treatment.

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Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

Cited by 8 publications

References 60 publications

Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Vorinostat (SAHA) and Breast Cancer: An Overview

Upregulated ONECUT2 impeded the efficacy of 5-FU treatment to relapsed patients and might be an emerging indicator of chemotherapy in gastric cancer

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