The growing area of biomaterial sciences has attracted broad attention in recent years in the development of peptide-based biocompatible materials with inherent therapeutic potentials. Here, we developed an Amoc (9-anthracenemethoxycarbonyl)-capped dipeptide-based biocompatible, injectable, thixotropic, and self-healable hydrogel. In vitro cytotoxicity of the hydrogel was investigated with the human embryonic kidney cell (HEK293) line. We observed that the synthesized peptide is noncytotoxic. The hydrogel showed an antibacterial efficacy against Gram-positive and Gram-negative bacteria. In vivo anti-inflammatory activity of the hydrogel was investigated using the rat air pouch model of acute inflammation. The major parameters considered for the anti-inflammatory study were exudate volume, total and differential white blood cell count, tissue histology, and lipid peroxidation assay. These experimental data suggest biocompatibility and potential therapeutic applications of peptide hydrogel in inflammation.
: Female breast cancer recently surpassed lung cancer and became the most commonly diagnosed cancer worldwide. As per the recent data from WHO, breast cancer accounts for one out of every 8 cancer cases diagnosed among an estimated 2.3 million new cancer cases. Breast cancer is the most prevailing cancer type among women causing the highest number of cancer-related mortality. It has been estimated that in 2020, 68,5000 women died due to this disease. Breast cancers have varying degrees of molecular heterogeneity; therefore, they are divided into various molecular clinical sub types. Recent reports suggest that type 2 diabetes (one of the common chronic diseases worldwide) is linked to the higher incidence, accelerated progression, and aggressiveness of different cancers; especially breast cancer. Breast cancer is hormone-dependent in nature and has a cross-talk with metabolism. A number of antidiabetic therapies are known to exert beneficial effects on various types of cancers, including breast cancer. However, only a few reports are available on the role of incretin-based antidiabetic therapies in cancer as a whole and in breast cancer in particular. The present review sheds light on the potential of incretin based therapies on breast cancer and explores the plausible underlying mechanisms. Additionally, we have also discussed the sub types of breast cancer as well as the intricate relationship between diabetes and breast cancer.
Background: Triple-negative breast cancer (TNBC) is known for Warburg-metabolism and defects in the mitochondria. AMP-dependent kinase (AMPK) activates the downstream transcription factors PGC-1α, PGC-1β, or FOXO1 which participate in mitochondrial biogenesis. 5-aminoimidazole-4-carboxamide riboside (AICAR) is an analog of adenosine monophosphate and is a direct activator of AMPK. Objectives: In the present study, we attempt to understand the influence of AICAR on TNBC cells MDA-MB-231 and the underlying changes in mitochondrial biogenesis, if any. Methods: We investigated AICAR induced changes in cell viability, apoptosis, migratory potential, and changes in the sensitivity of doxorubicin Results: In response to the treatment of MDA-MB-231 breast cancer cells with 750 µM of AICAR for 72 hours, followed by 48 hours in fresh media without AICAR, we observed a decrease in viability via MTT assay, reduction in cell numbers along with the apoptotic appearance, increased cell death by ELISA, decreased lactate in conditioned medium and decrease in migration by scratch and transwell migration assays. These changes in the cancer phenotype were accompanied by an increase in mitochondrial biogenesis, as observed by increased mitochondrial DNA to nuclear DNA ratio, a decrease in lactic acid concentration, increase in mitotracker green and red staining, and increased expression of transcription factors PGC-1α, NRF-1, NRF-2, and TFAM that contribute in mitochondrial biogenesis. Pre-treatment of cells with AICAR for 72 hours followed by 48 hours treatment with 1 µM doxorubicin showed an increased sensitivity to doxorubicin as assessed by MTT assay Conclusion: Our results show that AICAR exerts beneficial effects on TNBC cells possibly via switching off the Warburg metabolism and switching on the anti-Warburg metabolism through mitochondrial modulation
Triple-negative breast cancer (TNBC) cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria. On the other hand, dipeptidyl peptidase-IV (DPP-IV) inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis, but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line. We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase (AMPK), which activates the downstream transcription factors PGC-1α, PGC-1β, or FOXO1 for mitochondrial biogenesis; above-mentioned incretin-based therapies are also known to activate AMPK. This study evaluated the effects of sitagliptin, vildagliptin, and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis, were examined. Treatment with sitagliptin (100 µM), vildagliptin (100 µM), and exendin-4 (10 nM) for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay, cell migration by scratch, and transwell migration assays, accompanied with marginal reduction in cell numbers along with the apoptotic appearance, the rate of apoptosis, and decreased lactate content in conditioned medium. These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio, increased MitoTracker green and red staining, and increased expression of transcription factors PGC-1α, NRF-1, NRF-2, TFAM, and HO-1. Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1 µM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay. Thus, sitagliptin, vildagliptin, and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect. Therapeutic response was in the order of: sitagliptin > vildagliptin > exendin-4.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.