scholarly journals Non-cancer to anti-cancer: investigation of human ether-a-go-go-related gene potassium channel inhibitors as potential therapeutics

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Vaishali M. Patil ◽  
Anand Gaurav ◽  
Priyanka Garg ◽  
Neeraj Masand
Keyword(s):  
Cancer Cells ◽  
Preliminary Investigation ◽  
Drug Repurposing ◽  
Cancer Therapeutics ◽  
Late Stage Cancer ◽  
Anti Cancer ◽  
Reported Study ◽  
Binding Pockets ◽  
Cancer Inhibition

Abstract Background The expression of hERG K+ channels is observed in various cancer cells including epithelial, neuronal, leukemic, and connective tissue. The role of hERG potassium channels in regulating the growth and death of cancer cells include cell proliferation, survival, secretion of proangiogenic factors, invasiveness, and metastasis. Methods In the reported study, an attempt has been made to investigate some non-cancer hERG blockers as potential cancer therapeutics using a computational drug repurposing strategy. Preliminary investigation for hERG blockers/non-blockers has identified 26 potential clinically approved compounds for further studies using molecular modeling. Results The interactions at the binding pockets have been investigated along with the prioritization based on the binding score. Some of the identified potential hERG inhibitors, i.e., Bromocriptine, Darglitazone, and Troglitazone, have been investigated to derive the mechanism of cancer inhibition. Conclusions The proposed mechanism for anti-cancer properties via hERG blocking for some of the potential compounds is required to be explored using other experimental methodologies. The drug repurposing approach applied to investigate anti-cancer therapeutics may direct to provide a therapeutic solution to late-stage cancer and benefit a significant population of patients.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

Innovatory role of nanomaterials as bio-tools for treatment of cancer

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Khuram Shahzad Ahmad ◽  
Muntaha Talat ◽  
Shaan Bibi Jaffri ◽  
Neelofer Shaheen
Keyword(s):  
Cancer Treatment ◽  
Cancer Therapeutics ◽  
Physicochemical Characteristics ◽  
Global Scale ◽  
Current Review ◽  
Anti Cancer ◽  
Different Types ◽  
Cancerous Cells

AbstractConventional treatment modes like chemotherapy, thermal and radiations aimed at cancerous cells eradication are marked by destruction pointing the employment of nanomaterials as sustainable and auspicious materials for saving human lives. Cancer has been deemed as the second leading cause of death on a global scale. Nanomaterials employment in cancer treatment is based on the utilization of their inherent physicochemical characteristics in addition to their modification for using as nano-carriers and nano-vehicles eluted with anti-cancer drugs. Current work has reviewed the significant role of different types of nanomaterials in cancer therapeutics and diagnostics in a systematic way. Compilation of review has been done by analyzing voluminous investigations employing ERIC, MEDLINE, NHS Evidence and Web of Science databases. Search engines used were Google scholar, Jstore and PubMed. Current review is suggestive of the remarkable performance of nanomaterials making them candidates for cancer treatment for substitution of destructive treatment modes through investigation of their physicochemical characteristics, utilization outputs and long term impacts in patients.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

2021 ◽  
pp. 096032712110214
Author(s):  
Yansong Chen ◽  
Ye Tian ◽  
Gongsheng Jin ◽  
Zhen Cui ◽  
Wei Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glutamine Metabolism ◽  
Down Regulation ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

Stress responses as master keys to epigenomic changes in transcriptome and metabolome for cancer etiology and therapeutics

2021 ◽  
Author(s):  
Atanu Mondal ◽  
Apoorva Bhattacharya ◽  
Vipin Singh ◽  
Shruti Pandita ◽  
Albino Bacolla ◽  
...  
Keyword(s):  
Stress Response ◽  
Cancer Cells ◽  
Stress Responses ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
Molecular Architecture ◽  
Cancer Etiology ◽  
Treatment Scenario ◽  
Anti Cancer ◽  
Novel Therapeutic Strategies

From initiation through progression, cancer cells are subjected to a magnitude of endogenous and exogenous stresses, which aid in their neoplastic transformation. Exposure to these classes of stress induces imbalance in cellular homeostasis and, in response, cancer cells employ informative adaptive mechanisms to rebalance biochemical processes that facilitate survival and maintain their existence. Different kinds of stress stimuli trigger epigenetic alterations in cancer cells, which leads to changes in their transcriptome and metabolome, ultimately resulting in suppression of growth inhibition or induction of apoptosis. Whether cancer cells show a protective response to stress or succumb to cell death depends on the type of stress and duration of exposure. A thorough understanding of epigenetic and molecular architecture of cancer cell stress response pathways can unveil a plethora of information required to develop novel anti-cancer therapeutics. The present view highlights current knowledge about alterations in epigenome and transcriptome of cancer cells as a consequence of exposure to different physicochemical stressful stimuli such as reactive oxygen species (ROS), hypoxia, radiation, hyperthermia, genotoxic agents, and nutrient deprivation. Currently, an anti-cancer treatment scenario involving the imposition of stress on target cancer cells is gaining traction to augment or even replace conventional therapeutic regimens. Therefore, a comprehensive understanding of stress response pathways is crucial for devising and implementing novel therapeutic strategies.

Synthesis, characterization and anti-cancer applications of ytterbium doped gadolinium molybdate nanophosphor compound

2019 ◽  
Vol 9 (8) ◽  
pp. 882-894
Author(s):  
Jahnavi Rama Madhuri Kamaraju ◽  
Raghavendra Rao Kanchi ◽  
Rajesh Kumar Borra ◽  
Padma Suvarna Reniguntla ◽  
Satyanarayana Rentala
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Diagnosis ◽  
Breast Cancer Cells ◽  
Mri Contrast Agents ◽  
Gadolinium Complexes ◽  
Anti Cancer ◽  
Gadolinium Molybdate

Nanophosphor compounds with both diagnostic and therapeutic functions are potential for cancer diagnosis and treatment. Lanthanide complexes play a crucial role in cancer diagnosis and therapy. Gadolinium-complexes are commonly used as magnetic resonance imaging (MRI) contrast agents for cancer imaging. The role of a lanthanide, Ytterbium (Yb) in cancer treatment is not unknown. The present work focuses on finding the role of Yb when doped into Gadolinium complexes in cancer treatment. Our results demonstrate that Yb doped Gadolinium molybdate coated with biocompatible silica, effectively inhibited the viability of breast cancer cells after 24 and 48 h of treatment in in vitro, and in contrast the nanophosphor compounds did not affect the viability of healthy cells. Yb doped Gadolinium molybdate also up-regulated apoptotic genes in breast cancer cells. Hence we propose that Yb doped Gadolinium molybdate is a promising theranostic compound. To the best of our knowledge, this is the first report showing anti-cancer nature of Ytterbium-doped into Gadolinium nanophosphors.

scholarly journals Wnt Signaling in Cancer Metabolism and Immunity

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 904 ◽  
Author(s):  
Sara El-Sahli ◽  
Ying Xie ◽  
Lisheng Wang ◽  
Sheng Liu
Keyword(s):  
Wnt Signaling ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Tumor Initiating Cells ◽  
Tumor Plasticity ◽  
Anti Cancer ◽  
Wnt Ligands ◽  
Canonical Wnt

The Wingless (Wnt)/β-catenin pathway has long been associated with tumorigenesis, tumor plasticity, and tumor-initiating cells called cancer stem cells (CSCs). Wnt signaling has recently been implicated in the metabolic reprogramming of cancer cells. Aberrant Wnt signaling is considered to be a driver of metabolic alterations of glycolysis, glutaminolysis, and lipogenesis, processes essential to the survival of bulk and CSC populations. Over the past decade, the Wnt pathway has also been shown to regulate the tumor microenvironment (TME) and anti-cancer immunity. Wnt ligands released by tumor cells in the TME facilitate the immune evasion of cancer cells and hamper immunotherapy. In this review, we illustrate the role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.

Effects of a Novel Histone Deacetylase Inhibitor, PXD101, When Used as Monotherapy or in Combination with Bortezomib on Tumor Growth in Mouse Models of Human Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3483-3483 ◽  
Author(s):  
Richard A. Campbell ◽  
Eric Sanchez ◽  
Haiming Chen ◽  
Lauren Turker ◽  
Olivia Trac ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Mouse Models ◽  
Optimal Schedule ◽  
Cancer Therapeutics ◽  
Mouse Serum ◽  
Wide Range ◽  
Anti Cancer ◽  
Human Multiple Myeloma

Abstract Histone deacetylase (HDAC) inhibitors represent a new mechanistic class of anti-cancer therapeutics that inhibit HDAC enzymes and have been shown to have anti-proliferative effects in cancer cells (including drug resistance subtypes), induce apoptosis, inhibit angiogenesis, and sensitize cancer cells when combined with other available anti-cancer therapies. PXD101 is a novel investigational small molecule drug that selectively inhibits HDAC enzymes. In recent preclinical studies, PXD101 has been shown to have the potential to treat a wide range of solid and hematological malignancies either as a monotherapy or in combination with other active agents. In this study, we evaluated the activity of PXD101 on multiple myeloma samples when used as monotherapy or in combination with the proteasome inhibitor bortezomib. In vitro experiments indicated that PXD101 pretreatment (20 mM; 3h) sensitized RPMI-8226 human multiple myeloma cells to subsequent bortezomib exposure (5 nM; 72h). To examine PXD101 and bortezomib in vivo, two mouse models of human multiple myeloma were utilized (LAGλ-1 and LAGκ-1B). LAGλ-1 was generated from a patient resistant to melphalan therapy and LAGκ-1B from a patient who progressed on bortezomib treatment (Campbell et al, International Journal of Oncology 2006). SCID mice were implanted with LAGλ-1 or LAGκ-1B tumor fragments into the left superficial gluteal muscle. Tumors were allowed to grow for 14 days at which time human IgG levels were detectable in the mouse serum, and mice were randomly assigned into treatment groups. Groups consisted of Vehicle only, PXD101 alone (40 mg/kg), bortezomib alone (0.5 mg/kg), or PXD101 (40 mg/kg) + bortezomib (0.5 mg/kg). In one cohort, PXD101 and bortezomib were administered twice weekly (M, Th) and in another cohort PXD101 was administered 5 days a week (M-F) and bortezomib twice weekly (M, Th). When administered, PXD101 was given i.p twice daily and bortezomib once daily intravenously. The results of these animal experiments will provide preclinical information on the activity of PXD101 monotherapy and PXD101/bortezomib combination therapy on drug-resistant myeloma samples, and may help to define the optimal schedule for potential clinical evaluation of this drug combination.

scholarly journals The role of vitamin D3 in signaling pathways – potential anticancer properties of calcitriol and its analogues

2019 ◽  
Vol 73 ◽  
pp. 920-936
Author(s):  
Olga Wiecheć
Keyword(s):  
Vitamin D ◽  
Cancer Cells ◽  
Vitamin D3 ◽  
Active Form ◽  
Signalling Pathways ◽  
Active Metabolites ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Worse Prognosis

Vitamin D, for many years after the discovery, primarily was associated with bone metabolic processes. Currently, many studies indicate its beneficial effect in the prevention and treatment of many diseases, including cancer. However, deficiency of vitamin D is associated with greater tendency to get sick and worse prognosis in treatment, especially cancer. Calcitriol, an active form of vitamin D (1.25(OH)2D3) and its analogues have a pleiotropic activity, including anti-cancer properties. Many studies indicate, that the active forms of vitamin D3 may show anti-proliferative effects in cancer cells by inhibiting the cell cycle, inducing differentiation or leading to apoptosis and enhancing autophagy. Also, extremely important are the possibilities of reducing the invasiveness of tumours through the influence on angiogenesis or adhesion and others. Especially, the anti-cancer role of vitamin D3 is suggested in the case of tumors whose cells express VDR receptors. Interestingly, many cancer cells not only express the VDR receptors, but also due to the expression of CYP27B1 and CYP24A hydroxylases, they can regulate metabolism of calcitriol. Many of the studies using vitamin D3 show that calcitriol and its analogues, due to the influence on cancer cells, can play promising roles in anticancer therapies. Consider the broad pleiotropism of the action of active metabolites of vitamin D3 and the development of research in this field, the current work presents the effect of active forms of vitamin D on some signalling pathways and the regulation of selected proteins in various cancers.

scholarly journals RHAMM-target peptides inhibit invasion of breast cancer cells

2017 ◽  
Vol 1 (2) ◽  
pp. 138-148 ◽  
Author(s):  
Natalia Akentieva
Keyword(s):  
Breast Cancer ◽  
Confocal Microscopy ◽  
Cancer Cells ◽  
Mitotic Spindle ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Therapeutic Activity ◽  
Multiple Functions ◽  
Anti Cancer

Abstract RHAMM is hyaluronan- receptor with multiple functions in the cell, RHAMM is involved in proliferation, motility, migration, invasion, mitotic spindle formation in tumour cells. Therefore, RHAMM could be a relevant target for molecular targeted therapies against tumors.The role of RHAMM-target peptides in inhibition invasion for preventing breast cancer has not yet been investigated. Base on this, we analyzed the RHAMM-target peptides for their therapeutic activity against breast cancer cells. In the present study, we examined the effect of RHAMM-target peptides on the invasion of breast cancer cells (MDAMB- 231), using confocal microscopy. We shown that RHAMM-target peptides decreased formation of invadopodia of breast cancer cells. The treatment of breast cancer cells by RHAMM -target peptides inhibited the invasion up to 99 %. Additionally, RHAMM-target peptides induced the morphological changes of of breast cancer cells. Therefore, based on these results, we can conclude that RHAMM-target peptides may be potential anti-cancer agents.

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