Synthesis and Anticancer Properties of Novel Truncated Carbocyclic Nucleoside Analogues

2019 ◽  
Vol 18 (10) ◽  
pp. 1425-1431 ◽  
Author(s):  
Balija Sivakrishna ◽  
Sehbanul Islam ◽  
Amarendra Panda ◽  
Maddi Saranya ◽  
Manas K. Santra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Nucleoside Analogues ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties ◽  
Ovarian Cancer Cell Lines ◽  
Carbocyclic Nucleoside

Background: Modified nucleosides established a prime role as therapeutic drugs. Objective: Design and synthesis of novel truncated carbocyclic nucleoside with modified nucleobases and evaluation of their anticancer properties. Methods: Novel truncated carbocyclic nucleoside analogues were synthesized from a versatile starting material D-ribose. The synthetic route includes stereoselective Grignard reaction, Wittig olefination, ring closing metathesis, double bond hydrogenation and Mitsunobu nucleobase condensation as the key steps. Cytotoxicity was measured using MTT assay in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian cancer cell lines (IGROV1 and OVCAR8). Result & Conclusion: The synthesized compounds were characterized using spectroscopy techniques. The synthesized compounds induced cytotoxicity in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian cancer cell lines (IGROV1 and OVCAR8) while minimal effect on primary cell line. Among the eight analogues, 1b and 1d showed the highest cytotoxicity effect and induced autophagy mode of cell death. These compounds induced autophagy by inactivating AKT and mTOR pathway. In addition, PARP1 was found to be stabilized upon treatment with compound 1b and 1d and is one of the known markers associated with induction of autophagy through the AMPK/mTOR pathway after DNA damage. Taken together, these results suggest that compounds 1b and 1d inhibit cancer cell proliferation through mTOR inactivation-mediated induction of autophagy.

scholarly journals Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-xL and BID Protein Expression by Modulating Signaling Proteins Erk1/2 and STAT3, and DNA Damage in Breast and Colorectal Cancer Cell Lines

2017 ◽  
Vol 17 (2) ◽  
pp. 271-281 ◽  
Author(s):  
Abdulrahman Khazim Al-Asmari ◽  
Anvarbatcha Riyasdeen ◽  
Mozaffarul Islam
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Anticancer Agent ◽  
Cancer Cell Lines ◽  
Scorpion Venom ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties

Scorpion venoms efficiently block the normal neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. Besides its negative effect, venoms also possess some beneficial qualities for humans. They have also been shown to exhibit anticancer properties in various cancer types. This unique property of the venom as an anticancer agent is mainly a result of its role in initiating apoptosis and inhibiting several signaling cascade mechanisms that promote cancer cell proliferation and growth. In this study, we examine the effect of venom on phenotypic changes as well as changes at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both cancer cell lines on venom treatment. Additionally, there was decrease in IL-6, RhoC, Erk1/2, and STAT3 in venom-treated cell lines, providing strong evidence of its anticancer properties. Furthermore, decrease in the expression of antiapoptotic proteins and also upregulation of proapoptotic ones by these lines were observed on venom treatment. Moreover, a vivid picture of DNA damage was also detected on venom treatment. In conclusion, scorpion venom possesses significant potential as an anticancer agent against colorectal and breast cancer cell lines.

scholarly journals Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Britta Stapel ◽  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Peter Hillemanns ◽  
Stefan Bleich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Glucose Uptake ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Mortality Rates ◽  
Cancer Cell Lines ◽  
Breast And Ovarian Cancer ◽  
Ovarian Cancer Cell Lines

AbstractBreast cancer is the most prevalent malignancy amongst women worldwide while ovarian cancer represents the leading cause of death among gynecological malignancies. Women suffering from these cancers displayed heightened rates of major depressive disorder, and antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) is frequently recommended. Recently, narrative reviews and meta-analyses showed increased recurrence risks and mortality rates in SSRI-treated women with breast and ovarian cancer. We therefore examined whether three commonly prescribed SSRIs, fluoxetine, sertraline and citalopram, affect proliferation or glucose uptake of human breast and ovarian cancer cell lines characterized by different malignancies and metastatic potential. SSRI treatment or serotonin stimulation with therapeutically relevant concentrations over various time periods revealed no consistent dose- or time-dependent effect on proliferation rates. A marginal, but significant increase in glucose uptake was observed in SK-OV-3 ovarian cancer cells upon fluoxetine or sertraline, but not citalopram treatment. In three breast cancer cell lines and in two additional ovarian cancer cell lines no significant effect of SSRIs on glucose uptake was observed. Our data suggest that the observed increase in recurrence- and mortality rates in SSRI-treated cancer patients is unlikely to be linked to antidepressant therapies.

scholarly journals Structural Insight of the Anticancer Properties of Doxazosin on Overexpressing EGFR/HER2 Cell Lines

2021 ◽  
Author(s):  
Martiniano Bello ◽  
Miguel Ángel Vargas Mejía
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Conformational Changes ◽  
Hot Spot ◽  
Principal Component ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties

The selective α1-adrenergic receptor antagonist doxazosin is used for the treatment of hypertension. More recently, an experimental report demonstrated that this compound exhibits antiproliferative activity in breast cancer cell lines with similar inhibitory activity to gefitinib, a selective inhibitor of EGFR in the active state (EGFRAC). This experimental study provided evidence that doxazosin can be employed as an anticancer compound, however, the structural basis for its inhibitory properties is poorly understood at the atomic level. To gain insight about this molecule, molecular dynamics (MD) simulation with the molecular mechanics generalized Born surface area (MMGBSA) approach was employed to explore the structural and energetic features that guide the inhibitory properties of doxazosin and gefitinib in overexpressing EGFR/HER2 cell lines. Our result suggest that doxazosin exerts its inhibitory properties in breast cancer cell lines by targeting EGFR/HER2 but mainly HER2 in the inactive state (HER2IN), whereas gefitinib by targeting mainly EGFRAC, in line with previous literature. Decomposition of the binding affinity into individual contributions of HER2IN-doxazosin and EGFRAC-gefitinib systems detected hot spot residues but also showed polar interactions of Met801/Met793 with the quinazoline ring of both compounds. Principal component (PC) analysis revealed that the molecular recognition of the HER2IN-doxazosin system was linked to conformational changes but EGFRAC-gefitinib was not.

Blueberry anthocyanins and pyruvic acid adducts: anticancer properties in breast cancer cell lines

2010 ◽  
Vol 24 (12) ◽  
pp. 1862-1869 ◽  
Author(s):  
Ana Faria ◽  
Diogo Pestana ◽  
Diana Teixeira ◽  
Victor de Freitas ◽  
Nuno Mateus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Pyruvic Acid ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Anticancer Properties

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

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