Effect of Apatinib plus melatonin on vasculogenic mimicry formation by cancer stem cells from breast cancer cell line

Maroufi, Nazila Fathi; Rashidi, Mohsen; Vahedian, Vahid; Jahanbazi, Raheleh; Mostafaei, Sahar; Akbarzadeh, Maryam; Kazemzadeh, Hamid; Nejabati, Hamid-Reza; Isazadeh, Alireza; Rashidi, Mohammad‐Reza; Nouri, Mohammad

doi:10.1007/s12282-021-01310-4

Cited by 23 publications

(12 citation statements)

References 28 publications

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“…Regarding the transwell migration assay, the combinatory treatment diminished ( p < 0.05) the proportion of migrating cells to the same extent as the platinum(II) complex alone ( Figure 5 C). Other studies has also proven that indoleamine synergistically improves the antimigration properties of apatinib, a tyrosine kinase inhibitor thought to inhibit angiogenesis, in breast cancer stem cells derived from MDA-MB-231 cells [ 44 ], whereas novel melatonin–tamoxifen drug conjugates were shown to effectively inhibit migration in different breast cancer cell lines, including tamoxifen-resistant cells [ 45 ]. Nonetheless, even though melatonin has been described to inhibit cell invasion potential in MDA-MB-231 and MCF-7 breast cancer cell lines [ 46 ], indoleamine per se only evoked a moderate, non-significant impairment in the ability of TNBC cells to migrate ( Figure 5 A,B) and showed no effect in the transwell migration assay.…”

Section: Resultsmentioning

confidence: 99%

Pro-Apoptotic and Anti-Migration Properties of a Thiazoline-Containing Platinum(II) Complex in MDA-MB-231 Breast Cancer Cells: The Role of Melatonin as a Synergistic Agent

et al. 2022

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Triple-negative breast cancer (TNBC) is an aggressive cancer insensitive to hormonal and human epidermal growth factor receptor 2 (HER2)-targeted therapies and has a poor prognosis. Therefore, there is a need for the development of convenient anticancer strategies for the management of TNBC. In this paper, we evaluate the antitumoral potential of a platinum(II) complex coordinated with the ligand 2-(3,5-diphenylpyrazol-1-yl)-2-thiazoline (DPhPzTn), hereafter PtDPhPzTn, against the TNBC cell line MDA-MB-231, and compared its effect with both cisplatin and its less lipophilic counterpart PtPzTn, the latter containing the ligand 2-(pyrazol-1-yl)-2-thiazoline (PzTn). Then, the putative potentiating actions of melatonin, a naturally occurring antioxidant with renowned antitumor properties, on the tumor-killing ability of PtDPhPzTn were also checked in TNBC cells. Our results show that PtDPhPzTn presented enhanced cytotoxicity compared to both the classical drug cisplatin and PtPzTn. In addition, PtDPhPzTn was able to induce apoptosis, being more selective for MDA-MB-231 cells when compared to non-tumor breast epithelial MCF10A cells. Likewise, PtDPhPzTn produced moderate S phase arrest and greatly impaired the migration ability of MDA-MB-231 cells. Most importantly, the co-stimulation of TNBC cells with PtDPhPzTn and melatonin substantially enhanced apoptosis and markedly improved the anti-migratory action compared to PtDPhPzTn alone. Altogether, our findings provide evidence that PtDPhPzTn and melatonin could be potentially applied to breast cancer treatment as powerful synergistic agents.

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Section: Resultsmentioning

confidence: 99%

Pro-Apoptotic and Anti-Migration Properties of a Thiazoline-Containing Platinum(II) Complex in MDA-MB-231 Breast Cancer Cells: The Role of Melatonin as a Synergistic Agent

et al. 2022

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“…In vivo analysis also showed that melatonin significantly reduced tumor volume, with the tumor growth occurred in the hind flank. The effects of melatonin on the inhibition of estrogen-mediated proliferation of human ER-α positive BC cell lines (e.g., MCF-7) are well known [ 42 ]; however, despite several studies showing an anti-proliferative effect of melatonin on the triple-negative MDA-MB-231 cell line [ 43 , 44 ], others have reported that melatonin did not significantly inhibit in vitro proliferation of MDA-MB-231 cells [ 45 , 46 ]. One possible mechanism is that the effectiveness of melatonin may be dependent on the expression of the estrogen receptor [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Regulates the Daily Levels of Plasma Amino Acids, Acylcarnitines, Biogenic Amines, Sphingomyelins, and Hexoses in a Xenograft Model of Triple Negative Breast Cancer

Paula

Chuffa²,

Simão³

et al. 2022

IJMS

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Metabolic dysregulation as a reflection of specific metabolite production and its utilization is a common feature of many human neoplasms. Melatonin, an indoleamine that is highly available during darkness, has a variety of metabolic functions in solid tumors. Because plasma metabolites undergo circadian changes, we investigated the role of melatonin on the profile of amino acids (AAs), biogenic amines, carnitines, sphingolipids, and hexoses present in the plasma of mice bearing xenograft triple negative breast cancer (MDA-MB-231 cells) over 24 h. Plasma concentrations of nine AAs were reduced by melatonin, especially during the light phase, with a profile closer to that of non-breast cancer (BC) animals. With respect to acylcarnitine levels, melatonin reduced 12 out of 24 molecules in BC-bearing animals compared to their controls, especially at 06:00 h and 15:00 h. Importantly, melatonin reduced the concentrations of asymmetric dimethylarginine, carnosine, histamine, kynurenine, methionine sulfoxide, putrescine, spermidine, spermine, and symmetric dimethylarginine, which are associated with the BC metabolite sets. Melatonin also led to reduced levels of sphingomyelins and hexoses, which showed distinct daily variations over 24 h. These results highlight the role of melatonin in controlling the levels of plasma metabolites in human BC xenografts, which may impact cancer bioenergetics, in addition to emphasizing the need for a more accurate examination of its metabolomic changes at different time points.

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“…Resistance to the common chemotherapeutic drugs is a major obstacle to managing and treating human malignancies. Cancer cells acquire the ability to resist chemotherapeutic drugs through numerous mechanisms such as hypoxia, drug inactivation, microRNAs, drug efflux, drug-target alteration, extracellular matrix alterations, growth factors, and cytokines production and dysregulation pathways of cell death and survival (22,23).…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative Effects of Hydroxytyrosol Against Breast Cancer Cell Lines Through Induction of Apoptosis

et al. 2022

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Background: Due to high mortality of patients with metastatic breast cancer and limited strategies for management of this malignancy, development of novel therapeutic approaches and anti-cancer agents is essential. Objectives: In the present study, we investigated in vitro anti-proliferative effects of hydroxytyrosol, as a natural chemotherapeutic agent, against breast cancer cells MDA-MB-231 and MCF-7. Methods: The anti-proliferation activity of hydroxytyrosol on both MDA-MB-231 and MCF-7 breast cancer cells was evaluated by MTT assay. Apoptosis percentage was assessed by flow cytometry in the treated and untreated cancer cells. Moreover, the expression of three apoptotic genes (BAX, BCL2, and CASP3) was evaluated by Real-Time PCR in the treated cancer cells. Results: Our results indicated that hydroxytyrosol exerted an appropriate anti-proliferation activity on both MDA-MB-231 and MCF-7 cancer cells in a dose- and time-dependent manner. We observed a significant increase in apoptosis percentage in both treated cancer cells compared with untreated controls. In addition, hydroxytyrosol upregulated pro-apoptotic BAX and CASP3 genes while downregulated anti-apoptotic BCL2 gene. Conclusions: The findings of the present study suggested an appropriate anti-proliferation effect by hydroxytyrosol that may be due to apoptosis induction through modification of expression of apoptotic genes in breast cancer cells.

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Effect of Apatinib plus melatonin on vasculogenic mimicry formation by cancer stem cells from breast cancer cell line

Cited by 23 publications

References 28 publications

Pro-Apoptotic and Anti-Migration Properties of a Thiazoline-Containing Platinum(II) Complex in MDA-MB-231 Breast Cancer Cells: The Role of Melatonin as a Synergistic Agent

Pro-Apoptotic and Anti-Migration Properties of a Thiazoline-Containing Platinum(II) Complex in MDA-MB-231 Breast Cancer Cells: The Role of Melatonin as a Synergistic Agent

Melatonin Regulates the Daily Levels of Plasma Amino Acids, Acylcarnitines, Biogenic Amines, Sphingomyelins, and Hexoses in a Xenograft Model of Triple Negative Breast Cancer

Anti-proliferative Effects of Hydroxytyrosol Against Breast Cancer Cell Lines Through Induction of Apoptosis

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