scholarly journals BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway: analyses using a breast cancer cell line and tumoral xenograft model

Author(s):  
Yu
2020 ◽  
Vol 20 ◽  
Author(s):  
Maryam Safi ◽  
Habib Onsori ◽  
Mohammad Rahmati

Purpose: Breast cancer is the most frequent cancer among women and the most important cause of death. Surgery and chemotherapy are the common treatment of the breast cancer, but increasing drug resistance has created many challenges in its treatment. The present study aimed to investigate the anti-cancer function of free and nano-encapsulated hydroxytyrosol on the MCF-7 breast cancer cell line. Methods: The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hydroxytyrosol was synthesized, and the MTT assay was performed to evaluate the anti-proliferative and anti-tumor effects of both free and nanoencapsulated Hydroxytyrosol. After the extraction of RNA from the treated and control cancer cells, cDNA synthesis was performed and the expression of P21, P27, and Cyclin D1 genes were evaluated by Real-Time PCR. Results: The results of the study showed that free (12 ppm and 72 hours) and nano-encapsulate (10 ppm and 24 hours) hydroxytyrosol resulted in 50% death (IC50) of the cancer cells and increased by increasing the concentration and time. Also, free and nano-encapsulated hydroxytyrosol increased the expression of P21 and P27 genes and reduced the expression of Cyclin D1 in breast cancer cells. In general, the nano-encapsulated hydroxytyrosol showed more anticancer function than the free hydroxytyrosol. Conclusion: The present study illustrated that the hydroxytyrosol could lead to the cell death in MCF-7 breast cancer by regulating the cell cycle. Also, the nano-encapsulation of Hydroxytyrosol enhanced the Hydroxytyrosol anticancer function by PLGA-co-PAA. However, for more accurate results, further studies on animal models are necessary.


2021 ◽  
Vol 17 ◽  
pp. 174480692110240
Author(s):  
Silvia Gutierrez ◽  
James C Eisenach ◽  
M Danilo Boada

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.


2021 ◽  
Vol 14 (11) ◽  
Author(s):  
Mohammadreza Roshanazadeh ◽  
Hossein Babaahmadi Rezaei ◽  
Mojtaba Rashidi

Background: Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities. Objectives: This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB-231 breast cancer cell line. Methods: The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes. Results: The combination of 50 µM of que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone. Conclusions: Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy.


Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1531
Author(s):  
Hiromi Kurokawa ◽  
Hirofumi Matsui

Chemotherapy is cytotoxic to various cancer cells and as well as normal cells. Thus, treatments that demonstrate selective cytotoxicity for cancer cells are desired. The combination of chemotherapy and other cancer therapies can show synergic cytotoxicity, which may be a clue to the nature of the involved cancer cellar-specific damage. We previously reported a phenomenon whereby mitochondrial reactive oxygen species (mitROS) regulate the expression transporters involved in anticancer drug transport and mitROS production is increased by hyperthermia. Moreover, the uptake of 5-aminolevulinic acid (ALA) was enhanced by the increase in mitROS production. In this study, we investigated whether the combination of hyperthermia and ALA can enhance the cytotoxicity of doxorubicin. MitROS production and ALA-derived porphyrin accumulation by hyperthermia (HT) were increased in a murine breast cancer cell line. The expression of solute carrier 15A1 (SLC15A1) upregulated and an ATP-binding cassette subfamily G member 2 (ABCG2) downregulated by HT. Since SLC15A1 is an accumulating transporter for ALA, while ABCG2 is a porphyrin efflux transporter, porphyrin accumulation was enhanced. ABCG2 is also a doxorubicin efflux transporter. Thus, ALA treatment accelerates the intracellular concentration of porphyrin, which acts as a competitive inhibitor of doxorubicin. Indeed, the amount of intracellular doxorubicin was increased by a combination of HT and ALA. The cytotoxicity of doxorubicin was also enhanced. This enhancement was observed in the human breast cancer cell line while it was not seen in normal cells. The combination of HT and ALA treatment can enhance the cancer-specific cytotoxicity of doxorubicin.


2015 ◽  
Vol 67 (2) ◽  
pp. 571-581 ◽  
Author(s):  
Olivera Milosevic-Djordjevic ◽  
Darko Grujicic ◽  
Marina Radovic ◽  
Nenad Vukovic ◽  
Jovana Zizic ◽  
...  

Propolis has been used in folk medicine for centuries due to its healing properties. Ethanolic extracts of propolis (EEP) are rich sources of phenolic acid and flavonoids. Natural phenolic compounds may exert chemoprotective activity in cancer cells due to their ability to scavenge free radicals. The aim of this in vitro study was to investigate the genotoxic and anti-mutagenic effects of the EEP on human peripheral blood lymphocytes (PBLs) and their cytotoxic potential on the human breast cancer cell line (MDA-MB-231 cells). Both cell cultures were treated with six concentrations (1, 10, 50, 100, 250 and 500 ?g/ml) of EEP1 and EEP2, separately and in combination with mitomycin C (MMC). Our results show that the EEP1 and EEP2 samples of propolis after separate and combined treatments with MMC did not influence the nuclear division index (NDI). In the combined treatment, both tested EEPs significantly reduced MMC-induced micronuclei (MN) in PBLs. At 48 h after exposure of the MDA-MB-231 cell line to a combined treatment of EEP samples with MMC, the IC50 values were significantly reduced (23.79 and 19.13 ?g/ml, for EEP1+MMC and EEP2+MMC, respectively, in comparison to the single treatment. In conclusion, the tested ethanolic extracts of propolis exhibited a certain level of in vitro antimutagenic activity in PBLs from healthy subjects, and anticancer activity in breast cancer cell line. The presented findings suggest that the ethanolic extracts of propolis show potential in anticancer therapeutic strategy.


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