Colloidally Stabilized DSPE-PEG-Glucose/Calcium Phosphate Hybrid Nanocomposites for Enhanced Photodynamic Cancer Therapy via Complementary Mitochondrial Ca2+ Overload and Autophagy Inhibition DOI
Xuan Wang, Yunhao Li,

Xiongwei Deng

et al.

ACS Applied Materials & Interfaces, Journal Year: 2021, Volume and Issue: 13(33), P. 39112 - 39125

Published: Aug. 12, 2021

Autophagy inhibition could hinder the underlying protective mechanisms in course of tumor treatment. The advances autophagy have driven focus on functionalized nanoplatforms by combining current treatment paradigms with complementary for enhanced efficacy. Furthermore, Ca2+ overload is also a promising adjuvant target augmenting mitochondrial damage. In this view, and were first demonstrated as novel strategy suitable homing shortage photodynamic therapy (PDT). We constructed biodegradable tumor-targeted inorganic/organic hybrid nanocomposites (DPGC/OI) synchronously encapsulating IR780 Obatoclax biomineralization nanofilm method, which consists pH-triggered calcium phosphate (CP), long circulation phospholipid block copolymers 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-poly(ethylene glycol) (PEG)2000-glucose (DPG). presence hydrophilic PEG chain glucose transporter 1 (Glut-1) ligands, DPGC would become an effectively tumor-oriented nanoplatform. Subsequently, outstanding photosensitizer produce increased amounts toxic reactive oxygen species (ROS) after laser irradiation. Calcium (CP) nanogenerator generate at low pH to induce overload. dysfunction mitochondria enhance ROS. Based premise that degrade dysfunctional organelles sustain metabolism homeostasis, might participate resistance PDT, inhibitor mechanism from cancer cells negligible toxicity. Such PDT via be realized DPGC/OI.

Language: Английский

Recent Progress in the Development of Glucose Transporter (GLUT) Inhibitors DOI
Yuxuan Wang,

Zhiqiang Sun,

Zean Zhao

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Cancer cells exhibit an accelerated glucose uptake and glycolysis. The transmembrane of requires specific carrier proteins, such as transporters (GLUTs) sodium-coupled cotransporters (SGLTs). GLUTs transport independently the energy supply have become promising targets for cancer therapy. This Perspective mainly focuses on current research progress design strategy GLUT inhibitors, particularly those targeting class I (GLUT1–4). To best our knowledge, this is first systematic interpretation progress, opportunities, challenges faced in development inhibitors from a medicinal chemistry perspective. We hope that will provide insights into offering feasible approach to

Language: Английский

Citations

1
Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer DOI
Kalpana Tilekar,

Neha Upadhyay,

Cristina V. Iancu

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2020, Volume and Issue: 1874(2), P. 188457 - 188457

Published: Oct. 21, 2020

Language: Английский

Citations

58
Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract DOI Open Access
Jessica Ruzzolini, Silvia Peppicelli, Francesca Bianchini

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(2), P. 317 - 317

Published: Jan. 29, 2020

Oleuropein (Ole), the main bioactive phenolic component of Olea europaea L. has recently attracted scientific attention for its several beneficial properties, including anticancer effects. This study is intended to investigate whether an olive leaf extract enriched in Ole (OLEO) may counteract aerobic glycolysis exploited by tumor cells. We found that OLEO decreased melanoma cell proliferation and motility. was also able reduce rate human cells without affecting oxidative phosphorylation. reduction associated with a significant decrease glucose transporter-1, protein kinase isoform M2 monocarboxylate transporter-4 expression, possible drivers such inhibition. Extending other histotypes, we observed metabolic effects are not confined melanoma, but confirmed colon carcinoma, breast cancer chronic myeloid leukemia. In conclusion, represents natural product effective reducing glycolytic metabolism different types, revealing extended inhibitory activity be well suited complementary anti-cancer therapy.

Language: Английский

Citations

51
Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer DOI
Leila Kooshki,

Parisa Mahdavi,

Sajad Fakhri

et al.

BioFactors, Journal Year: 2021, Volume and Issue: 48(2), P. 359 - 383

Published: Nov. 1, 2021

Abstract Anticancer drugs are not purely effective because of their toxicity, side effects, high cost, inaccessibility, and associated resistance. On the other hand, cancer is a complex public health problem that could intelligently adopt different signaling pathways alter body's metabolism to escape from immune system. One strategies metastasize modifying pH in tumor microenvironment, ranging between 6.5 6.9. As powerful determiner, lactate responsible for this acidosis. It involved stimulation, including innate adaptive immunity, apoptotic‐related factors (Bax/Bcl‐2, caspase), glycolysis (e.g., GLUT‐1, PKM2, PFK, HK2, MCT‐1, LDH). Lactate metabolism, turn, interconnected with several dysregulated mediators, PI3K/Akt/mTOR, AMPK, NF‐κB, Nrf2, JAK/STAT, HIF‐1α. Because lactate's emerging critical role, targeting production its transporters important preventing managing tumorigenesis. Hence, exploring developing novel promising anticancer agents minimize human cancers urgent. Based on numerous studies, natural secondary metabolites as multi‐target alternative compounds health‐promoting properties possess more effectiveness low effects than conventional agents. Besides, mechanism multi‐targeted sources related cancer‐associated cross‐talked factors. This review focuses metabolism/transporters, lactate‐associated glycolytic pathways. mediators also targeted by products. Accordingly, plant‐derived introduced therapies combating through modulating

Language: Английский

Citations

50
Akt Isoforms: A Family Affair in Breast Cancer DOI Open Access
Alakananda Basu, Christoffer Briggs Lambring

Cancers, Journal Year: 2021, Volume and Issue: 13(14), P. 3445 - 3445

Published: July 9, 2021

Akt, also known as protein kinase B (PKB), belongs to the AGC family of kinases. It acts downstream phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, survival, metabolism, tumor growth metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer plays an important role development progression cancer. There are three closely related members Akt family, namely Akt1(PKBα), Akt2(PKBβ) Akt3(PKBγ). Although isoforms share similar structures, they exhibit redundant, distinct well opposite functions. While target for therapy, understanding isoform-specific function critical effectively this pathway. However, our perception regarding how contribute genesis changes we gain new knowledge. purpose review article analyze current literatures on functions

Language: Английский

Citations

47
Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer DOI Creative Commons

Jurnal Reang,

Prabodh Chander Sharma, Vijay Kumar Thakur

et al.

Biomolecules, Journal Year: 2021, Volume and Issue: 11(8), P. 1130 - 1130

Published: July 31, 2021

Cancer, a fatal disease, is also one of the main causes death worldwide. Despite various developments to prevent and treat cancer, side effects anticancer drugs remain major concern. Ascorbic acid an essential vitamin required by our bodies for normal physiological function has antioxidant activity. Although body cannot synthesize ascorbic acid, it abundant in nature through foods other natural sources exists as nutritional food supplement. In drug development, played important role inhibiting development cancer mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving epigenetic regulator, regulating expression HIF cells. Several analogues have been produced date The current review summarizes mechanisms behind acid’s antitumor activity, presents compilation its derivatives biological activity agents, discusses delivery systems such liposomes, nanoparticles patents on agents.

Language: Английский

Citations

47
Modular Design of High-Brightness pH-Activatable Near-Infrared BODIPY Probes for Noninvasive Fluorescence Detection of Deep-Seated Early Breast Cancer Bone Metastasis: Remarkable Axial Substituent Effect on Performance DOI Creative Commons
Peng Wu, Yu Zhu,

Senyao Liu

et al.

ACS Central Science, Journal Year: 2021, Volume and Issue: 7(12), P. 2039 - 2048

Published: Dec. 9, 2021

We herein report a series of high-brightness pH-activatable near-infrared (NIR) BODIPY probes for high-contrast intravital imaging deep-seated early breast cancer bone metastasis by harnessing the axial substituent effect. These exhibit tunable pKa, higher brightness, and antiquenching capabilities in aqueous solution, which can be simultaneously adjusted steric substituents. The optimized probe BODO-3 bearing dimethyl substituents exhibited pKa value 5.6 brighter NIR fluorescence under tumor acidic pH, showing 10.3-fold 6.5-fold enhanced brightness (εΦ) at pH 5.5 6.5, respectively. Due to with brilliant emission 700 nm allows deep optical penetrations 5 8 mm 6.5 4.5, Meanwhile, covalent functionalization glucose (BODO-3-Glu) could further enhance its soft tissue vivo. Notably, bisphosphonate (BODO-3-PO3H2 ) allowed successful targeting visualization metastases high normal contrast 8/1, outperforming X-rays detection. This strategy may provide insights designing activatable detecting tumors metastases.

Language: Английский

Citations

43
Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance DOI Open Access
Lei Pan, Wenzhou Wang,

Marisela Sheldon

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3390 - 3390

Published: June 28, 2023

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies recent years have revealed molecular mechanisms by which regulates cancer. To date, despite a few metabolism-based drugs being tested or en route to clinical trials, no targeting metabolism pathways yet approved treat Here, we review the roles action progression drug resistance. In addition, summarize currently available inhibitors discuss challenges opportunities this pathway for treatment.

Language: Английский

Citations

22
Understanding Breast Cancer Aggressiveness and Its Implications in Diagnosis and Treatment DOI Open Access

Nader Afifi,

Carlos A. Barrero

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 1375 - 1375

Published: Feb. 9, 2023

Breast cancer (BC) is the most common form of in women worldwide [...].

Language: Английский

Citations

19
Betulinic acid in the treatment of breast cancer: Application and mechanism progress DOI

Huijuan Mu,

Yuli Sun, Bo Yuan

et al.

Fitoterapia, Journal Year: 2023, Volume and Issue: 169, P. 105617 - 105617

Published: July 19, 2023

Language: Английский

Citations

19