New S‐substituted‐3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B‐RAF signaling pathway DOI Creative Commons

Safaa E. Seif,

Wagnat W. Wardakhan, Rasha A. Hassan

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(7)

Published: Oct. 18, 2024

Abstract Novel 3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐ d ]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b , 5f 9c showed significant antitumor at single dose with mean growth inhibition 55.62%, 55.79%, 71.40%, respectively. These compounds further investigated HCT‐116, colon line, FHC, normal line. Compound the highest IC 50 = 0.904 ± 0.03 µM SI 20.42 excelling doxorubicin which scored 2.556 0.09 6.19. was also most potent B‐RAF WT mutated V600E 0.145 0.005 0.042 0.002 µM, respectively in comparison vemurafenib 0.229 0.008 0.038 0.001 The cycle analysis that increased population induced an arrest HCT‐116 cells G0‐G1 stage 1.23‐fold. Apoptosis evaluation compound displayed 18.18‐fold elevation total apoptosis to control. content caspase‐3 by 3.52‐fold versus A molecular modeling study determined binding profile interaction active site.

Language: Английский

Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium DOI Open Access
Aleksandar Ćirović,

Soisungwan Satarug

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1851 - 1851

Published: Feb. 3, 2024

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption involves transporters for essential metals, notably iron zinc. These determine body burden because only a minuscule amount can be excreted each day. International Agency Research on Cancer listed as human lung carcinogen, but current evidence suggests that effects cancer risk extend beyond lung. A two-year bioassay demonstrated caused neoplasms in multiple tissues mice. Also, several non-tumorigenic cells transformed to malignant when they were exposed sublethal dose prolonged time. does not directly damage DNA, it influences gene expression through interactions with metals various proteins. present review highlights epidemiological studies connect enhanced neoplastic diseases chronic Cd. Special emphasis given impact stores Cd, its implications breast prevention highly susceptible groups women. Resistance cell death phenotypes acquired during Cd-induced transformation, under vitro conditions, are briefly discussed. potential role ZnT1 efflux transporter cellular acquisition tolerance cytotoxicity highlighted.

Language: Английский

Citations

15
Oxidative Stress and ROS Link Diabetes and Cancer DOI Creative Commons

Homer S. Black

Journal of Molecular Pathology, Journal Year: 2024, Volume and Issue: 5(1), P. 96 - 119

Published: March 1, 2024

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths globally, whereas cancer is the second leading cause death in U.S. T2DM a known risk factor many cancers. Reactive oxygen species (ROS)-altered metabolic and signaling pathways link to cancer. These reprogrammed contribute diabetic complications, impact redox balance (oxidative stress), have differential roles early late stages A respiratory chain that highly reduced (as under hyperglycemic conditions) or if cofactors accumulate, ROS are greatly elevated. may mutations mitochondrial DNA (mtDNA) result further elevations. The amplification results activation PKC, an overarching pathway activates MAPK with subsequent regulation several factors pathophysiological manifestations An upregulation PKC leads deregulation NF-kß, which regulates PKB/P13/Akt orchestrates cell survival, growth, proliferation, glucose metabolism manifested It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin-stimulated transport uptake, disrupting contributing development T2DM. Dyslipidemia hallmark ROS-induced lipid peroxidation systemic inflammation, producing inflammatory prostaglandins, cytokines, chemokines tumor rapid modulation immunity. dual role makes antioxidant therapy precarious be responsible controversial results. system delivers directly mitochondria useful inhibiting formation during pre-diabetic stage, must halted later retard metastasis.

Language: Английский

Citations

9
Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium DOI Open Access
Aleksandar Ćirović,

Soisungwan Satarug

Published: Jan. 15, 2024

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet the main non-workplace Cd exposure source other than smoking. The intestinal absorption involves transporters for iron, zinc, copper, and calcium. These metal essentially determine body burden because only 0.001-0.005% accumulated in can be excreted urine each day. International Agency Research on Cancer listed as a human lung carcinogen. Current evidence, however, suggests that may increase prevalence many types cancer, notably lung, liver, breast, pancreas, kidney. A two-year bioassay mimics lifelong demonstrates caused neoplasms multiple tissues mice. Also, several non-tumorigenic cell lines underwent malignant transformation, when they were exposed to sublethal dose prolonged time. does not directly damage DNA, but it profoundly affect gene expression through its interactions with various proteins, thus viewed transcription modulator. present review highlights epidemiological studies connected enhanced risk neoplastic diseases chronic Cd. Special emphasis impact iron stores rate Cd, implications breast cancer prevention highly susceptible subpopulation groups women. Resistance death phenotypes acquired during Cd-induced cancer-cell under vitro conditions, are briefly discussed. potential role ZnT1 efflux transporter cellular acquisition tolerance cytotoxicity highlighted.

Language: Английский

Citations

5
Is Cancer Metabolism an Atavism? DOI Open Access
Éric Fanchon, Anastasis Stephanou

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2415 - 2415

Published: June 29, 2024

The atavistic theory of cancer posits that emerges and progresses through the reversion cellular phenotypes to more ancestral types with genomic epigenetic changes deactivating recently evolved genetic modules activating ancient survival mechanisms. This aims at explaining known hallmarks paradox cancer’s predictable progression despite randomness mutations. Lineweaver colleagues proposed Serial Atavism Model (SAM), an enhanced version theory, which suggests involves multiple reversions where cells regress evolutionary stages, losing traits first reactivating primitive ones later. Warburg effect, upregulate glycolysis lactate production in presence oxygen instead using oxidative phosphorylation, is one key feature SAM. It associated metabolism living on Earth before oxygenation atmosphere. review addresses question whether can be considered as reversion. By analyzing several characteristics metabolism, we reach conclusion this does not provide adequate conceptual frame for research. Cancer spans a whole spectrum metabolic states cannot fully explained by sequential state. Moreover, interrogate nature discuss its within framework

Language: Английский

Citations

1
New S‐substituted‐3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B‐RAF signaling pathway DOI Creative Commons

Safaa E. Seif,

Wagnat W. Wardakhan, Rasha A. Hassan

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(7)

Published: Oct. 18, 2024

Abstract Novel 3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐ d ]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b , 5f 9c showed significant antitumor at single dose with mean growth inhibition 55.62%, 55.79%, 71.40%, respectively. These compounds further investigated HCT‐116, colon line, FHC, normal line. Compound the highest IC 50 = 0.904 ± 0.03 µM SI 20.42 excelling doxorubicin which scored 2.556 0.09 6.19. was also most potent B‐RAF WT mutated V600E 0.145 0.005 0.042 0.002 µM, respectively in comparison vemurafenib 0.229 0.008 0.038 0.001 The cycle analysis that increased population induced an arrest HCT‐116 cells G0‐G1 stage 1.23‐fold. Apoptosis evaluation compound displayed 18.18‐fold elevation total apoptosis to control. content caspase‐3 by 3.52‐fold versus A molecular modeling study determined binding profile interaction active site.

Language: Английский

Citations

1