scholarly journals Insulin/IGF Axis in Breast Cancer: Clinical Evidence and Translational Insights

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 125
Author(s):  
Federica Biello ◽  
Francesca Platini ◽  
Francesca D’Avanzo ◽  
Carlo Cattrini ◽  
Alessia Mennitto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Evidence ◽  
Fat Tissue ◽  
Endocrine Effects ◽  
Anti Cancer ◽  
Literature Evidence ◽  
Inflammatory State ◽  
Key Drivers ◽  
Host Metabolism ◽  
Worse Prognosis

Background: Breast cancer (BC) is the most common neoplasm in women. Many clinical and preclinical studies investigated the possible relationship between host metabolism and BC. Significant differences among BC subtypes have been reported for glucose metabolism. Insulin can promote tumorigenesis through a direct effect on epithelial tissues or indirectly by affecting the levels of other modulators, such as the insulin-like growth factor (IGF) family of receptors, sex hormones, and adipokines. The potential anti-cancer activity of metformin is based on two principal effects: first, its capacity for lowering circulating insulin levels with indirect endocrine effects that may impact on tumor cell proliferation; second, its direct influence on many pro-cancer signaling pathways that are key drivers of BC aggressiveness. Methods: In the present review, the interaction between BC, host metabolism, and patients’ prognosis has been reviewed across available literature evidence. Conclusions: Obesity, metabolic syndrome, and insulin resistance are all involved in BC growth and could have a relevant impact on prognosis. All these factors act through a pro-inflammatory state, mediated by cytokines originated in fat tissue, and seem to be related to a higher risk of BC development and worse prognosis.

Molecular Mechanisms of Thymoquinone as Anticancer agent

2020 ◽  
Vol 23 ◽  
Author(s):  
Fatma Ismail Alhmied ◽  
Ali Hassan Alammar ◽  
Bayan Mohammed Alsultan ◽  
Marooj Alshehri ◽  
Faheem Hyder Pottoo
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Human Breast Cancer ◽  
Phase Cell ◽  
Cycle Phase ◽  
Human Breast ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Anti Cancer

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

A Review on Phytopharmaceutical shaving Concomitant Experimental Anti-Diabetic and Anti-Cancer Effects as Potential Sources for Targeted Therapies Against Insulin Mediated Breast Cancer Cell Invasion and Migration

2020 ◽  
Vol 16 ◽  
Author(s):  
Vibhavana Singh ◽  
Rakesh Reddy ◽  
Antarip Sinha ◽  
Venkatesh Marturi ◽  
Shravani Sripathi Panditharadyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medicinal Plants ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

: Diabetes and breast cancer are pathophysiologically similar and clinically established diseases that co-exist with a wider complex similar molecular signalling and having similar set of risk factors. Insulin plays a pivotal role for invasion and migration of breast cancer cells. Several ethnopharmacological evidences light the concomitant anti-diabetic and anti-cancer activity of medicinal plant and phytochemicals against breast tumor of patients with diabetes. This present article reviewed the findings on medicinal plants and phytochemicals with concomitant anti-diabetic and anti-cancer effects reported in scientific literature to facilitate the development of dual-acting therapies against diabetes and breast cancer. The schematic tabular form of published literatures on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals against diabetes and breast tumor that could be explored further for the discovery of therapies for controlling of breast cancer cell invasion and migration in patient with diabetes.

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents

2019 ◽  
Vol 19 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Faeze Khalili ◽  
Sara Akrami ◽  
Malihe Safavi ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
High Yield ◽  
Breast Cancer Cell Lines ◽  
Pyridine Derivatives ◽  
One Pot ◽  
Standard Drug ◽  
Three Component Reaction ◽  
Anti Cancer

Background: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. Objective: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. Methods: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. Results: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. Conclusion: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

Understanding Molecular Process and Chemotherapeutics for the Management of Breast Cancer.

2020 ◽  
Vol 14 ◽  
Author(s):  
Abhishek Kumar ◽  
Neeraj Masand ◽  
Vaishali M. Patil
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Molecular Classification ◽  
Neoplastic Disease ◽  
Molecular Process ◽  
The Past ◽  
Anti Cancer ◽  
Molecular Etiology ◽  
Near Future

Abstract: Breast cancer is the most common and highly heterogeneous neoplastic disease comprised of several subtypes with distinct molecular etiology and clinical behaviours. The mortality observed over the past few decades and the failure in eradicating the disease is due to the lack of specific etiology, molecular mechanisms involved in initiation and progression of breast cancer. Understanding of the molecular classes of breast cancer may also lead to new biological insights and eventually to better therapies. The promising therapeutic targets and novel anti-cancer approaches emerging from these molecular targets that could be applied clinically in the near future are being highlighted. In addition, this review discusses some of the details of current molecular classification and available chemotherapeutics

scholarly journals A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2873
Author(s):  
Shu-Chun Chang ◽  
Chin-Sheng Hung ◽  
Bo-Xiang Zhang ◽  
Tsung-Han Hsieh ◽  
Wayne Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Mrna Level ◽  
Breast Carcinogenesis ◽  
E3 Ligases ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Cell Progression ◽  
F Box Protein ◽  
Cancer Activity

Breast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiquitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregulation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, suggesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpression reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza. Shiran ◽  
Davar Amani ◽  
Abolghasem Ajami ◽  
Mahshad Jalalpourroodsari ◽  
Maghsoud Khalizadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Volume ◽  
Serum Levels ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Paraffin Oil ◽  
Anti Cancer ◽  
Before And After ◽  
Ifn Γ

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

scholarly journals The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide

Angiogenesis ◽  
2021 ◽  
Author(s):  
Juan Pablo Robles ◽  
Magdalena Zamora ◽  
Lourdes Siqueiros-Marquez ◽  
Elva Adan-Castro ◽  
Gabriela Ramirez-Hernandez ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Clinical Evidence ◽  
Therapeutic Potential ◽  
Peripartum Cardiomyopathy ◽  
Loss Of Function ◽  
Functional Determinant ◽  
Melanoma Tumor ◽  
Linear Motif ◽  
Anti Cancer ◽  
Orally Active

AbstractThe hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.

Sign in / Sign up

Export Citation Format

Share Document