Abstract 6381: NBS-1120: An e-NSAID with potent anti-cancer activity targets cell cycle proteins by generating polysulfides

Author(s):  
Jan J. Scicinski ◽  
Kenneth Olsen ◽  
Janet Stephens ◽  
Khosrow Kashfi
Author(s):  
Haroon Khan ◽  
Fabiana Labanca ◽  
Hammad Ullah ◽  
Yaseen Hussain ◽  
Nikolay T. Tzvetkov ◽  
...  

AbstractOver the years, the attention towards the role of phytochemicals in dietary natural products in reducing the risk of developing cancer is rising. Cancer is the second primary cause of mortality worldwide. The current therapeutic options for cancer treatment are surgical excision, immunotherapy, chemotherapy, and radiotherapy. Unfortunately, in case of metastases or chemoresistance, the treatment options become very limited. Despite the advances in medical and pharmaceutical sciences, the impact of available treatments on survival is not satisfactory. Recently, natural products are a great deal of interest as potential anti-cancer agents. Among them, phenolic compounds have gained a great deal of interest, thanks to their anti-cancer activity. The present review focuses on the suppression of cancer by targeting BRCA gene expression using dietary polyphenols, as well as the clinical aspects of polyphenolic agents in cancer therapy. They regulate specific key processes involved in cancer progression and modulate the expression of oncogenic proteins, like p27, p21, and p53, which may lead to apoptosis, cell cycle arrest, inhibition of cell proliferation, and, consequently, cancer suppression. Thus, one of the mechanisms underlying the anti-cancer activity of phenolics involves the regulation of tumor suppressor genes. Among them, the BRCA genes, with the two forms (BRCA-1 and BRCA-2), play a pivotal role in cancer protection and prevention. BRCA germline mutations are associated with an increased risk of developing several types of cancers, including ovarian, breast, and prostate cancers. BRCA genes also play a key role in the sensitivity and response of cancer cells to specific pharmacological treatments. As the importance of BRCA-1 and BRCA-2 in reducing cancer invasiveness, repairing DNA damages, oncosoppression, and cell cycle checkpoint, their regulation by natural molecules has been examined.


Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 792 ◽  
Author(s):  
Dhanasekhar Reddy ◽  
Ranjith Kumavath ◽  
Preetam Ghosh ◽  
Debmalya Barh

Cardiac glycosides (CGs) are a diverse family of naturally derived compounds having a steroid and glycone moiety in their structures. CG molecules inhibit the α-subunit of ubiquitous transmembrane protein Na+/K+-ATPase and are clinically approved for the treatment of cardiovascular diseases. Recently, the CGs were found to exhibit selective cytotoxic effects against cancer cells, raising interest in their use as anti-cancer molecules. In this current study, we explored the underlying mechanism responsible for the anti-cancer activity of Lanatoside C against breast (MCF-7), lung (A549), and liver (HepG2) cancer cell lines. Using Real-time PCR, western blot, and immunofluorescence studies, we observed that (i) Lanatoside C inhibited cell proliferation and induced apoptosis in cell-specific and dose-dependent manner only in cancer cell lines; (ii) Lanatoside C exerts its anti-cancer activity by arresting the G2/M phase of cell cycle by blocking MAPK/Wnt/PAM signaling pathways; (iii) it induces apoptosis by inducing DNA damage and inhibiting PI3K/AKT/mTOR signaling pathways; and finally, (iv) molecular docking analysis shows significant evidence on the binding sites of Lanatoside C with various key signaling proteins ranging from cell survival to cell death. Our studies provide a novel molecular insight of anti-cancer activities of Lanatoside C in human cancer cells.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44093 ◽  
Author(s):  
Min-Wu Chao ◽  
Chun-Han Chen ◽  
Ya-Ling Chang ◽  
Che-Ming Teng ◽  
Shiow-Lin Pan

2017 ◽  
Vol 23 (27) ◽  
pp. 6518-6521 ◽  
Author(s):  
Peter V. Simpson ◽  
Ilaria Casari ◽  
Silvano Paternoster ◽  
Brian W. Skelton ◽  
Marco Falasca ◽  
...  

2009 ◽  
Vol 602 (2-3) ◽  
pp. 203-214 ◽  
Author(s):  
Bhumika Thati ◽  
Andy Noble ◽  
Bernadette S. Creaven ◽  
Maureen Walsh ◽  
Malachy McCann ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Nurul Azwa Abd Wahab ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu

Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 µM) compared to curcumin (EC50: DU 145; 34.25 ± 2.7 µM and PC-3; 27.77 ± 6.4 µM). In addition, MS13 exhibited significant anti-proliferative activity against AIPC cells compared to curcumin in a dose- and time-dependent manner. Morphological observation, increased caspase-3 activity, and reduced Bcl-2 protein levels in these cells indicated that MS13 induces apoptosis in a time- and dose-dependent. Moreover, MS13 effectively inhibited the migration of DU 145 and PC-3 cells. Our results suggest that cell cycle-apoptosis and PI3K pathways were the topmost significant pathways impacted by MS13 activity. Our findings suggest that MS13 may demonstrate the anti-cancer activity by modulating DEGs associated with the cell cycle-apoptosis and PI3K pathways, thus inhibiting cell proliferation and cell migration as well as inducing apoptosis in AIPC cells.


2019 ◽  
Vol 6 (4) ◽  
pp. 58-68
Author(s):  
T. I. Fetisov ◽  
K. I. Kirsanov ◽  
A. A. Borunova ◽  
M. N. Zatsepina ◽  
E. A. Lesovaya ◽  
...  

Background. Curaxin CBL0137 is a novel non-genotoxic compound with anti-cancer activity based on CBL0137 ability of non-covalent interaction with DNA causing histone chaperone FACT relocation. Anti-cancer activity of this drug was demonstrated previously on the wide panel of solid cancer models in vitro and in vivo.Objectives. Estimation of anticancer effects of CBL0137 on the acute myeloblastic leukemia cells (THP-1) and acute lymphoblastic leukemia (CCRF-CEM).Materials and methods. CBL0137 cytotoxicity was analyzed using the MTT test, the effects on the cell cycle and the induction of apoptosis was assessed by flow cytometry, the activity of signaling pathways in cells treated with CBL0137 was determined by real-time polymerase chain reaction.Results. Cell treatment with CBL0137 led to cell cycle arrest and apoptosis induction. In the study of CBL0137 effect on target gene clusters of 10 signal transduction pathways involved in the pathogenesis of acute leukemia we have showed that CBL0137 inhibited the expression of down-stream genes of WNT and Hedgehog signaling in both cell lines. In THP-1 cells we also observed the inhibition of the expression of PPARγ target and hypoxia-activated genes. In CCRF-CEM cells CBL0137 also induced the expression of Notch signaling target genes.Conclusion. The antitumor activity of CBL0137 was demonstrated on acute leukemia cell cultures, the drug possesses cytotoxicity, causes cell cycle arrest and activation of apoptosis. Significant changes in the expression of efferent gene clusters of several signaling pathways were observed in the cells treated with CBL0137.


2021 ◽  
Author(s):  
Alireza Afshar ◽  
Arezoo Khoradmehr ◽  
Masoud Zare ◽  
Neda Baghban ◽  
Gholamhossein Mohebbi ◽  
...  

Abstract Background: Avicennia marina, the gray mangrove, is an herbal source of bioactive anti-cancer compounds.Purpose: The present study aimed to evaluate phytochemical compositions of ethanol and ethyl acetate extracts of A. marina leaves and experimental study and computational modeling of their anti-cancer activity on breast, ovarian and cervical cancer cell lines.Study design: Phytochemical analysis, computational modeling and experimental in vitro evaluationMethods: Phytochemical analysis and GC-MS analysis were used to detect phenolic and flavonoid contents in ethanol and ethyl acetate extracts of A. marina leaves. Cell proliferation, viability, cycle and western blot assays of the extracts were performed on MCF-7, OVCAR3, and HeLa. Computational modeling done to detect effective compounds.Results: The extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anti-cancer and anti-proliferative compounds were detected. Moreover, after treatment of MCF-7, OVCAR3, and HeLa, separately, the MTT assay, cell proliferation assay, and cell viability assays showed anti-proliferative activity, decreasing of cell population and decreasing cell viability, respectively. In addition, the cell cycle analysis showed that the S phase of the cell cycle increased in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis.Conclusion: The extracts of A. marina leaves have anti-cancer effects on breast, ovarian and cervical cancer cells via cell cycle arrest or apoptotic mechanisms.


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