Synthesis and antitumor evaluation of glycyrrhetinic acid‐dithiocarbamate hybrids DOI
Jiahong Su, Xingyue Wang, Sha Li

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 358(1)

Published: Nov. 11, 2024

Abstract Glycyrrhetinic acid (GA) is a naturally occurring triterpene compound. The aim of this study was to employ the pharmacophore hybrid strategy merge GA with various dithiocarbamates and obtain novel compounds better antitumor activities. We present two‐step synthetic protocol wherein derivative underwent reaction carbon disulfide secondary amines in one‐pot manner under mild conditions, facilitating preparation series structurally GA‐dithiocarbamate derivatives. Bioassay screening revealed that representative compound 3c demonstrated capacity reduce mitochondrial membrane potential Hep3B Huh‐7 cells, induce nuclear apoptosis, inhibit invasion migration, prompt both early late apoptosis. Furthermore, our research findings indicated apoptotic phenomenon may be associated expression Bcl‐2, Bax, Bak, PARP, cleaved‐PARP proteins. Utilizing network pharmacology for predicting core targets signaling pathways hepatocellular carcinoma (HCC) treatment involved employing molecular docking models demonstrate high affinity between target protein. In conjunction Western blot analysis, impact HCC through PI3K‐AKT‐mTOR pathway.

Language: Английский

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin‐Induced Resistance and Stemness in Human Lung Cancer A549 Cells DOI Creative Commons
Luxin Fan, Xiaodong Wang,

Cheng Cong-cong

et al.

Evidence-based Complementary and Alternative Medicine, Journal Year: 2023, Volume and Issue: 2023(1)

Published: Jan. 1, 2023

The survival rate of lung cancer patients remains low largely due to chemotherapy resistance during treatment, and stem cells (CSCs) may hold the key targeting this resistance. Cisplatin is a drug commonly used in yet mechanisms intrinsic cisplatin have not been determined because CSCs are hard identify. In paper, we proposed mechanism relating function ursolic acid (UA), new drug, reversing regulated by CSCs. Human cell line A549 was selected as model treated become cisplatin-resistant (A549-CisR), which less sensitive showed an enhanced capability tumor sphere formation. Furthermore, A549-CisR expression, levels pluripotent transcription factors Oct-4, Sox-2, c-Myc were increased, activation Jak2/Stat3 signaling pathway promoted. When UA applied cells, restrained inhibition pathway, reduced enrichment turn, reversed cells. Hence, potential antitumor be able inhibit CSC population inhibiting Jak2-Stat3 preventing cisplatin.

Language: Английский

Citations

1
Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway DOI Creative Commons
Yangyang Lu,

Chunyang Zhu,

Yixin Ding

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: May 16, 2023

Abstract Cephalanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata , is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer unknown. CEP inhibited cellular activity AGS and HGC27 cell lines in this study. induced apoptosis, reduced Bcl-2 expression, increased cleaved caspase 3, 9, Bax, Bad expression. caused G2 cycle arrest cyclin D1 cyclin-dependent kinases 2 (CDK2) Meanwhile, it oxidative stress, decreased mitochondrial membrane potential, enhanced reactive oxygen species (ROS) accumulation cells. Mechanistically, Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor (Nrf2) increasing transcription Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase (HMOX1), glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, combined analysis targeted energy metabolism RNA sequencing revealed that could alter levels metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic pyruvic thereby altering In addition, significantly tumor growth MFC BALB/c nude mice vivo consistent with vitro findings. Overall, can induce stress by regulating Nrf2/Keap1 metabolism, resulting anti-ovarian effects. Our findings suggest potential application treatment.

Language: Английский

Citations

1
The Inhibitory Mechanisms of Capsaicin Against Colorectal Cancer DOI

Saabira Banu Sahubar Sadik,

Ashok Kumar Pandurangan

Published: Jan. 1, 2024

Language: Английский

Citations

0
Synthesis and antitumor evaluation of glycyrrhetinic acid‐dithiocarbamate hybrids DOI
Jiahong Su, Xingyue Wang, Sha Li

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 358(1)

Published: Nov. 11, 2024

Abstract Glycyrrhetinic acid (GA) is a naturally occurring triterpene compound. The aim of this study was to employ the pharmacophore hybrid strategy merge GA with various dithiocarbamates and obtain novel compounds better antitumor activities. We present two‐step synthetic protocol wherein derivative underwent reaction carbon disulfide secondary amines in one‐pot manner under mild conditions, facilitating preparation series structurally GA‐dithiocarbamate derivatives. Bioassay screening revealed that representative compound 3c demonstrated capacity reduce mitochondrial membrane potential Hep3B Huh‐7 cells, induce nuclear apoptosis, inhibit invasion migration, prompt both early late apoptosis. Furthermore, our research findings indicated apoptotic phenomenon may be associated expression Bcl‐2, Bax, Bak, PARP, cleaved‐PARP proteins. Utilizing network pharmacology for predicting core targets signaling pathways hepatocellular carcinoma (HCC) treatment involved employing molecular docking models demonstrate high affinity between target protein. In conjunction Western blot analysis, impact HCC through PI3K‐AKT‐mTOR pathway.

Language: Английский

Citations

0