The Cytotoxic Effect of Curcumin in Rhabdomyosarcoma Is Associated with the Modulation of AMPK, AKT/mTOR, STAT, and p53 Signaling DOI Open Access
Sara Salucci, Alberto Bavelloni,

Anna Bartoletti Stella

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(3), P. 740 - 740

Published: Feb. 1, 2023

Approximately 7% of cancers arising in children and 1% those adults are soft tissue sarcomas (STS). Of these malignancies, rhabdomyosarcoma (RMS) is the most common. RMS survival rates using current therapeutic protocols have remained largely unchanged past decade. Thus, it imperative that main molecular drivers tumorigenesis defined so more precise, effective, less toxic therapies can be designed. Curcumin, a common herbal supplement derived from plants Curcuma longa species, has an exceptionally low dietary biotoxicity profile demonstrated anti-tumorigenic benefits vitro. In this study, activity curcumin was assessed cell lines used to identify major pathways responsible for curcumin's effects. Curcumin treatment resulted cycle arrest, inhibited migration colony forming potential, induced apoptotic death. Proteome profiler array analysis primarily influenced flux through AKT-mammalian target rapamycin (mTOR), signal transducer activator transcription (STAT), AMP-dependent kinase (AMPK), p53 associated subtype-specific manner. strategic, combinational targeting may present best option treat group tumors.

Language: Английский

Oxidative Stress in Cancer DOI Creative Commons
John D. Hayes, Albena T. Dinkova‐Kostova, Kenneth D. Tew

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(2), P. 167 - 197

Published: July 9, 2020

Language: Английский

Citations

1854
Targeting the JAK/STAT pathway in solid tumors DOI Open Access
Zoya Qureshy, Daniel E. Johnson, Jennifer R. Grandis

et al.

Journal of Cancer Metastasis and Treatment, Journal Year: 2020, Volume and Issue: 2020

Published: Aug. 21, 2020

Aberrant activation of signal transducer and activator transcription (STAT) proteins is associated with the development progression solid tumors. However, as factors, these are difficult to target directly. In this review, we summarize role targeting Janus kinases (JAKs), upstream activators STATs, a strategy for decreasing STAT in Preclinical studies tumor cell line models show that JAK inhibitors decrease activation, proliferation, survival;

Language: Английский

Citations

116
Targeting transcription cycles in cancer DOI
Stephin J. Vervoort, Jennifer R. Devlin, Nicholas Kwiatkowski

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 22(1), P. 5 - 24

Published: Oct. 21, 2021

Language: Английский

Citations

102
Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer DOI Creative Commons

Sareshma Sudhesh Dev,

Syafiq Asnawi Zainal Abidin, Reyhaneh Farghadani

et al.

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 15, 2021

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role cancer progression suitable therapeutic target. The use small molecule inhibitors however, has been crippled by the emergence resistance, highlighting need for pleiotropic anti-cancer agent can replace or be used combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive mainly due potent effects, extensive range targets minimal toxicity. Out numerous documented curcumin, RTKs appear one main nodes curcumin-mediated inhibition. Many studies have found curcumin influences activation their downstream signaling pathways resulting increased decreased proliferation migration both vitro vivo. This review focused on how exhibits effects through inhibition MAPK, PI3K/Akt, JAK/STAT, NF-κB pathways. Combination were also analysed emphasis common molecular targets.

Language: Английский

Citations

96
Role of Rad51 and DNA repair in cancer: A molecular perspective DOI
Erik Laurini, Domenico Marson,

Alice Fermeglia

et al.

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 208, P. 107492 - 107492

Published: Jan. 27, 2020

Language: Английский

Citations

88
The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis DOI Creative Commons
Theresa D. Ahrens, Sara R. Bang-Christensen, Amalie M. Jørgensen

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Aug. 26, 2020

Circulating tumor cells (CTCs) are accessible by liquid biopsies via an easy blood draw. They represent not only the primary site, but also potential metastatic lesions, and could thus be attractive supplement for cancer diagnostics. However, analysis of rare CTCs in billions normal is still technically challenging novel specific CTC markers needed. The formation metastasis a complex process supported numerous molecular alterations, might found focusing on this process. One example changes cell glycocalyx, which network surface composed carbohydrate structures. Proteoglycans important glycocalyx components consist protein core covalently attached long glycosaminoglycan chains. A few assays have already utilized proteoglycans both enrichment CTCs. biological function clinical has been studied detail so far. Therefore, present review describes proteoglycan functions during cascade to highlight their importance We outline current approaches based targeting cores or Lastly, we briefly discuss technical aspects, should considered studying proteoglycans.

Language: Английский

Citations

75
Targeting the JAK-STAT pathway in autoimmune diseases and cancers: A focus on molecular mechanisms and therapeutic potential DOI
Hong‐Tai Tzeng, I‐Tsu Chyuan, Jenn‐Haung Lai

et al.

Biochemical Pharmacology, Journal Year: 2021, Volume and Issue: 193, P. 114760 - 114760

Published: Sept. 4, 2021

Language: Английский

Citations

69
Crosstalk between PRLR and EGFR/HER2 Signaling Pathways in Breast Cancer DOI Open Access
Raghuveer Kavarthapu, Rajakumar Anbazhagan, Maria Dufau

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(18), P. 4685 - 4685

Published: Sept. 18, 2021

Prolactin receptor (PRLR) and epidermal growth factor (EGFR/ERBB) signaling pathways activated by prolactin (PRL) (EGF), have a major role in the mammary gland development etiology of breast cancer, respectively. ER+ tumors comprise up to 75% all cancers 10% these are HER2+. Elevated levels PRLR tumors, high circulating PRL increased expression ERBB1/2 patients that become resistant endocrine therapy shown be associated with higher risk cancer progression. In this review, we examine crosstalk between activation unliganded ERα, cyclin-D1 other oncogenic factors (MYC, FOS, JUN) cancer. PRL/PRLR EGF/EGFR induces phosphorylation ERα through MEK/MAPK PI3K/AKT pathways. cells via PRLR/JAK2 can also induce ERBB2/HER2, which turn activates downstream RAS/MEK/ERK pathway required for phosphorylation. EGFR, independent PRL/PRLR, activate STAT5 indirectly c-SRC drive target genes involved cell proliferation survival. The HER2, where HER2 an alternative route transcription ER genes. We believe overexpression EGFR/HER2 could maximize actions their ligands, further promoting malignancy. This explain resistance resulting tumor growth.

Language: Английский

Citations

66
Glutamine Synthetase as a Therapeutic Target for Cancer Treatment DOI Open Access

Go Woon Kim,

Dong Hoon Lee,

Yu Hyun Jeon

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1701 - 1701

Published: Feb. 8, 2021

The significance of glutamine in cancer metabolism has been extensively studied. Cancer cells consume an excessive amount to facilitate rapid proliferation. Thus, depletion occurs various types, especially poorly vascularized cancers. This makes synthetase (GS), the only enzyme responsible for de novo synthesizing glutamine, essential metabolism. In cancer, GS exhibits pro-tumoral features by supporting nucleotide synthesis. Furthermore, is highly expressed tumor microenvironment (TME) and provides cells, allowing maintain sufficient level catabolism. Glutamine catabolism, opposite reaction synthesis GS, well known cell proliferation via contributing biosynthesis molecules energy production. Either anabolism or catabolism a critical function depending on complex nature this review, we focus role variety types microenvironments highlight mechanism at transcriptional post-translational levels. Lastly, discuss therapeutic implications targeting cancer.

Language: Английский

Citations

59
Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers DOI Creative Commons
Cassandra A. Hathaway, Megan S. Rice, Laura C. Collins

et al.

Breast Cancer Research, Journal Year: 2023, Volume and Issue: 25(1)

Published: March 7, 2023

Abstract Background Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the receptor (PRLR) can activate transcription factor STAT5, thus, we examined association between plasma and risk by tumor expression of PRLR, upstream kinase JAK2. Methods Using data from 745 cases 2454 matched controls in Nurses’ Health Study, conducted polytomous logistic regression examine (> 11 ng/mL vs. ≤ ng/mL) measured within 10 years diagnosis PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), JAK2 (pJAK2; C) expression. Analyses were separately premenopausal ( n = 168 cases, 765 controls) postmenopausal women 577 1689 controls). Results In women, levels > positively tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) pSTAT5-C 1.64, 1.01–2.65), but not that negative these markers 0.98, 0.65–1.46 OR 0.73, 0.43–1.25; p-heterogeneity 0.06 0.02, respectively). This was stronger when both 2.88, 1.14–7.25). No observed or pJAK2 (positive negative) among women. Among irrespective pSTAT5, (all ≥ 0.21). Conclusion We did observe clear differences pJAK2, although associations pSTAT5 only. While additional studies are needed, this suggests may act on human development through alternative pathways.

Language: Английский

Citations

27