A Review on Anti-Tumor Mechanisms of Coumarins

Wu, Yi; Xu, Jing; Liu, Yiting; Zeng, Yiyu; Wu, Guojun

doi:10.3389/fonc.2020.592853

Cited by 132 publications

(88 citation statements)

References 49 publications

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“…In particular, coumarin derivatives have shown a variety of biological activities such as CK2 inhibitors 39 , EGFR 40 , PI3K-AKT-mTOR signalling inhibitors 41–43 . Furthermore, their anticancer potential, tumour targets, diverse mechanisms of action as well as their advantages and disadvantages have been recently reviewed 44 . In continuation with our previous work and prompted by these considerations, to further explore the influences of structural modifications on the coumarin and psoralene core on the activity and selectivity towards membrane-bound hCA isozyme, we have designed and synthesised a small library of methyl-2-[4-methyl-2-oxo-7–(2-oxo-2-arylethoxy)-8-propylchromen-3-yl]acetate and 2–(5-methyl-7-oxo-3-aryl-9-propyl-7H-furo[3,2-g]chromen-6-yl)acetic acid derivatives were a propyl group in the position 8 or 9 has been introduced compared to the previously synthesised derivatives.…”

Section: Introductionmentioning

confidence: 99%

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

Meleddu

Deplano

Maccioni

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors.

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Section: Introductionmentioning

confidence: 99%

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

Meleddu

Deplano

Maccioni

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Coumarins and their derivatives have been regarded as an important family of anticancer lead compounds, which exhibit diverse effects such as anti-proliferation, antiinvasion, anti-metastasis, anti-angiogenesis and inducing apoptosis. The various mechanisms of their anticancer action have been widely explored [22][23][24][25][26][27][28], including inhibition of carbonic anhydrase, PI3K/AKT/mTOR signaling pathway, microtubule polymerization, monocarboxylate transporters, hypoxia-inducible factor-1, acting on apoptosis proteins, inhibiting tumor multidrug resistance, and regulating ROS.…”

Section: Discussionmentioning

confidence: 99%

Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro

Zhang

Tan

et al. 2021

Molecules

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Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.

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“…Mechanistically, the data demonstrated that LCT-3d induced gastric cell apoptosis through DR5-mediated mitochondrial pathway. The activation of Caspase family proteins is an important event leading to cell apoptosis (21). At the early stage of apoptosis, Caspase 3 and Caspase 9 were activated, and they served as biomarker proteins of apoptosis (22).…”

Section: Discussionmentioning

confidence: 99%

LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells

Wang

Wu²,

Yu³

et al. 2021

Front. Oncol.

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Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis via mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can’t reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.

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A Review on Anti-Tumor Mechanisms of Coumarins

Cited by 132 publications

References 49 publications

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro

LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells

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