scholarly journals Insilico and Invitro optimization of Naringin and rutin molecules targeting DNA damage in breast cancer cells

2021 ◽  
Author(s):  
Pravin Badhe ◽  
Vivek Nanaware ◽  
Ashwini Badhe
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Dermal Fibroblast ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Human Dermal Fibroblast

Discovering the molecular mechanisms of DNA damage response pathways has led to new therapeutic approaches in oncology. Our study optimized DNA damage-targeting molecules naringin and rutin in breast cancer cells. Our study involved MTT assays for detection of its toxicity and proliferative activity in breast cancer cells and normal cancer cells. Our studies determined the molecules' antioxidant properties using the DPPH assay. The role in reducing free radicals has been evaluated using a variety of free radical scavenging activity assays. Further evaluation of the molecules was carried out by high alkaline comet assay (pH>13) to test for genotoxicity. Human Dermal Fibroblast cells (2DD) (1x105 cells/ml) and breast cancer cells (MDA-MB-231) were pre-incubated with Naringin and Rutin (10 microMolar) for one hour. In normal cells, rutin and naringin molecules do not cause genotoxicity, but they cause DNA damage in breast cancer cells when they are diluted to 10microMolar. The results from our study indicate that both molecules cause 60-70% DNA damage in breast cancer cells.

scholarly journals Strobilanthes heyneanus root extract as a potential source for antioxidant and antimicrobial activity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vijayakumar Sundaram ◽  
Selvaraju Sadhasivam ◽  
Sivaraj Chandrasekaran ◽  
Raaman Nanjian ◽  
Arjun Pandian
Keyword(s):  
Dermal Fibroblast ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Fibroblast Cell ◽  
Phytochemical Analysis ◽  
Root Extract ◽  
Scavenging Activity ◽  
Medicinal Uses

Abstract Background Strobilanthes heyneanus (Nilgirianthus heyneanus) belongs to the family Acanthaceae that contains many species with potential for diverse medicinal uses. It is also called ‘Karun kurinji’ and is commonly found in the South-West regions of India. The species are commonly used in rheumatic complaints, sprain of the ankle, and hernia. The objectives of the study were to evaluate the antioxidant activity, phytochemical analysis, and antibacterial activities of the root extract of S. heyneanus. Results The radical scavenging and reduction assays such as DPPH● radical and OH● radical scavenging assays, as well as phosphomolybdenum reduction and Fe3+ reducing power assays, were determined for the root extract. The highest DPPH● radical scavenging activity was 88.23 ± 1.32 at 120 μg/mL concentration, and the calculated IC50 was 38.52 μg/mL concentration. The highest OH● radical scavenging activity was 51.28 ± 1.06 at 120 μg/mL concentration, and the calculated IC50 was 51.28 μg/mL concentration. The highest ABTS●+ radical scavenging activity was 91.28 ± 1.12 at 30 μg/mL concentration, and the calculated IC50 was 33.92 μg/mL concentration. The highest phosphomolybdenum reduction was 87.43 ± 0.90 at 120 μg/mL concentration, and the calculated RC50 was 24.74 μg/mL concentration. The highest Fe3+ reduction was 89.38 ± 0.98 at 120 μg/mL concentration, and the calculated RC50 was 31.06 μg/mL concentration. The antibacterial activity of S. heyneanus showed the highest zone of inhibition of 24 mm for Salmonella typhi with 500 μg/mL concentration. The cytotoxicity limits of the root extracts were tested by MTT assay using human dermal fibroblast cell lines, reflecting > 90% cell viability at a concentration of 500 μg/mL. Conclusions The current study showed that the root extract of S. heyneanus has better antioxidant properties and potential anti-bacterial compounds. The phytochemical analysis of the root extract showed the presence of alkaloids, steroids, terpenoids, phenols, flavonoids, tannins, saponins, glycosides, and carbohydrates, which are responsible for the antibacterial root extract of S. heyneanus synergistically.

scholarly journals A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Mammosphere Formation ◽  
Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

Down regulation of Pinkbar/pAKT and MMP2/MMP9 expression in MDA-MB-231 breast cancer cells as potential targets in cancer therapy by hAMSCs secretome

2021 ◽  
Author(s):  
Termeh Shakery ◽  
Fatemeh Safari
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
3D Cell Culture ◽  
Therapeutic Effects ◽  
Down Regulation ◽  
Egfr Signaling Pathway

Breast cancer (BC) is one of the most causes of cancer-related death among women worldwide. Cancer therapy based on stem cells was considered as a novel and promising platform. In present study, we explored the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) through Pinkbar (planar intestinal-and kidney-specific BAR domain protein), pAKT, and matrix metalloproteinases including MMP2, MMP9 on MDA-MB-231 breast cancer cells. To do so, we employed a co-culture system using 6 well plates transwell with a diameter of 0.4 μm pore sized. After 72h hAMSCs-treated MDA-MB-231 breast cancer cells, the expression of Epidermal growth factor receptor (EGFR), and c-Src (a key mediator in EGFR signaling pathway), Pinkbar, pAKT, MMP2, and MMP9 was analyzed by using quantitative real time PCR (qRT-PCR) and western blot methods. Based on using 2D and 3D cell culture models, the significant reduction of tumor cell growth and motility through down regulation of EGFR, c-Src, Pinkbar, pAKT, MMP2, and MMP9 in MDA-MB-231 breast cancer cells was shown. Also, the induction of cellular apoptosis also found. Our finding indicates that the hAMSCS secretome has therapeutic effects on cancer cells. To identify the details of the molecular mechanisms, more experiments will be required.

Calcineurin regulates the stability and activity of estrogen receptor α

2021 ◽  
Vol 118 (44) ◽  
pp. e2114258118
Author(s):  
Takahiro Masaki ◽  
Makoto Habara ◽  
Yuki Sato ◽  
Takahiro Goshima ◽  
Keisuke Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
The Stability ◽  
Positive Breast Cancer

Estrogen receptor α (ER-α) mediates estrogen-dependent cancer progression and is expressed in most breast cancer cells. However, the molecular mechanisms underlying the regulation of the cellular abundance and activity of ER-α remain unclear. We here show that the protein phosphatase calcineurin regulates both ER-α stability and activity in human breast cancer cells. Calcineurin depletion or inhibition down-regulated the abundance of ER-α by promoting its polyubiquitination and degradation. Calcineurin inhibition also promoted the binding of ER-α to the E3 ubiquitin ligase E6AP, and calcineurin mediated the dephosphorylation of ER-α at Ser294 in vitro. Moreover, the ER-α (S294A) mutant was more stable and activated the expression of ER-α target genes to a greater extent compared with the wild-type protein, whereas the extents of its interaction with E6AP and polyubiquitination were attenuated. These results suggest that the phosphorylation of ER-α at Ser294 promotes its binding to E6AP and consequent degradation. Calcineurin was also found to be required for the phosphorylation of ER-α at Ser118 by mechanistic target of rapamycin complex 1 and the consequent activation of ER-α in response to β-estradiol treatment. Our study thus indicates that calcineurin controls both the stability and activity of ER-α by regulating its phosphorylation at Ser294 and Ser118. Finally, the expression of the calcineurin A–α gene (PPP3CA) was associated with poor prognosis in ER-α–positive breast cancer patients treated with tamoxifen or other endocrine therapeutic agents. Calcineurin is thus a promising target for the development of therapies for ER-α–positive breast cancer.

scholarly journals ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3415
Author(s):  
Ge Dong ◽  
Gui Ma ◽  
Rui Wu ◽  
Jinming Liu ◽  
Mingcheng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Progesterone Receptors ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Mammosphere Formation

Breast cancer is a common malignancy, but the understanding of its cellular and molecular mechanisms is limited. ZFHX3, a transcription factor with many homeodomains and zinc fingers, suppresses prostatic carcinogenesis but promotes tumor growth of liver cancer cells. ZFHX3 regulates mammary epithelial cells’ proliferation and differentiation by interacting with estrogen and progesterone receptors, potent breast cancer regulators. However, whether ZFHX3 plays a role in breast carcinogenesis is unknown. Here, we found that ZFHX3 promoted the proliferation and tumor growth of breast cancer cells in culture and nude mice; and higher expression of ZFHX3 in human breast cancer specimens was associated with poorer prognosis. The knockdown of ZFHX3 in ZFHX3-high MCF-7 cells decreased, and ZFHX3 overexpression in ZFHX3-low T-47D cells increased the proportion of breast cancer stem cells (BCSCs) defined by mammosphere formation and the expression of CD44, CD24, and/or aldehyde dehydrogenase 1. Among several transcription factors that have been implicated in BCSCs, MYC and TBX3 were transcriptionally activated by ZFHX3 via promoter binding, as demonstrated by luciferase-reporter and ChIP assays. These findings suggest that ZFHX3 promotes breast cancer cells’ proliferation and tumor growth likely by enhancing BCSC features and upregulating MYC, TBX3, and others.

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