Analogues of Orphan Nuclear Receptor Small Heterodimer Partner Ligand and Apoptosis Inducer (<i>E</i>)-4-[3-(1-Adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic Acid. 2. Impact of 3-Chloro Group Replacement on Inhibition of Proliferation and Induction of Apoptosis of Leukemia and Cancer Cell Lines

Xia, Zebin; Correa, Ricardo G.; Das, Jayanta; Farhana, Lulu; Castro, David J.; Yu, Jinghua; Oshima, Robert G.; Fontana, Joseph A.; Reed, John C.; Dawson, Marcia I.

doi:10.1021/jm2011436

Cited by 16 publications

(3 citation statements)

References 44 publications

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“…Multiple studies revealed that when SHP specific ligands, 5-Cl-AHPN & 3-Cl-AHPC used alone or in combination, decreased cell proliferation and increased cell cycle arrest, and apoptosis in KG-1 AML cells [ 127 , 128 ]. Kim et al (2009) reported that treatment of leukemic (U937) cells with differentiation agents such as phorbol esters (PMA) have increased the levels of SHP, p21 WAF1 , and p65 of NF-κB subunits, suggesting how the expression of SHP increases the cellular survival of differentiating monocytes by transcriptional regulation of target genes of cell survival and differentiation [ 126 ].…”

Section: Nrs In Hmmentioning

confidence: 99%

Exploring the nexus of nuclear receptors in hematological malignancies

Manickasamy,

Sajeev,

BharathwajChetty

et al. 2024

Cell. Mol. Life Sci.

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Hematological malignancies (HM) represent a subset of neoplasms affecting the blood, bone marrow, and lymphatic systems, categorized primarily into leukemia, lymphoma, and multiple myeloma. Their prognosis varies considerably, with a frequent risk of relapse despite ongoing treatments. While contemporary therapeutic strategies have extended overall patient survival, they do not offer cures for advanced stages and often lead to challenges such as acquisition of drug resistance, recurrence, and severe side effects. The need for innovative therapeutic targets is vital to elevate both survival rates and patients' quality of life. Recent research has pivoted towards nuclear receptors (NRs) due to their role in modulating tumor cell characteristics including uncontrolled proliferation, differentiation, apoptosis evasion, invasion and migration. Existing evidence emphasizes NRs' critical role in HM. The regulation of NR expression through agonists, antagonists, or selective modulators, contingent upon their levels, offers promising clinical implications in HM management. Moreover, several anticancer agents targeting NRs have been approved by the Food and Drug Administration (FDA). This review highlights the integral function of NRs in HM's pathophysiology and the potential benefits of therapeutically targeting these receptors, suggesting a prospective avenue for more efficient therapeutic interventions against HM. Graphical abstract

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Section: Nrs In Hmmentioning

confidence: 99%

Exploring the nexus of nuclear receptors in hematological malignancies

Manickasamy,

Sajeev,

BharathwajChetty

et al. 2024

Cell. Mol. Life Sci.

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“…Besides the cinnamic acid hybrids mentioned above, some other cinnamic acid conjugates also showed certain antiproliferative activity against various cancer cell lines. [ 63–77 ] For example, hybrid 34 ((2 R ,3 S ,3a S ,6a R )−2‐(( R )‐hydroxy(phenyl)methyl)−5‐oxohexahydrofuro[3,2‐ b ]furan‐3‐yl cinnamate; IC 50 : 0.12–0.85 µM, MTT assay) was highly potent against K562, Jurkat, MCF‐7, and HeLa cancer cell lines and the activity was slightly lower than that of doxorubicin (IC 50 : 0.03–0.25 µM). [ 77 ] However, the majority of the rest of the cinnamic acid hybrids were far inferior to the references drugs in terms of antiproliferative activity.…”

Section: Cinnamic Acid Hybridsmentioning

confidence: 99%

Cinnamic acid hybrids as anticancer agents: A mini‐review

Feng

Cheng

et al. 2022

Archiv der Pharmazie

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Cancer, as a long‐lasting and dramatic disease, affects almost one‐third of human beings globally. Chemotherapeutics play an important role in cancer treatment, but multidrug resistance and severe adverse effects have already become the main causes of failure in tumor chemotherapy. Therefore, it is an urgent need to develop novel chemotherapeutics. Cinnamic acid contains a ubiquitous α,β‐unsaturated acid moiety presenting potential therapeutic effects in the treatment of cancer as these derivatives could act on cancer cells by diverse mechanisms of action. Accordingly, cinnamic acid derivatives are critical scaffolds in discovering novel anticancer agents. This review provides a comprehensive overview of cinnamic acid hybrids as anticancer agents. The structure–activity relationship, as well as the mechanisms of action, are also discussed, covering articles published from 2012 to 2021.

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“…This ligand-dependent activation was shown to repress certain CYP enzymes involved in bile acid regulation. Additional studies are also exposing further potential synthetic ligands that could be utilized to modulate SHP activity and its repressive functions (Xia et al, 2011, 2012). …”

Section: Atypical Receptors and Receptor-like Proteinsmentioning

confidence: 99%

Xenobiotic-sensing nuclear receptors involved in drug metabolism: a structural perspective

Wallace

Redinbo

2012

Drug Metabolism Reviews

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Xenobiotic compounds undergo a critical range of biotransformations performed by the phase I, II, and III drug-metabolizing enzymes. The oxidation, conjugation, and transportation of potentially harmful xenobiotic and endobiotic compounds achieved by these catalytic systems are significantly regulated, at the gene expression level, by members of the nuclear receptor (NR) family of ligand-modulated transcription factors. Activation of NRs by a variety of endo- and exogenous chemicals are elemental to induction and repression of drug-metabolism pathways. The master xenobiotic sensing NRs, the promiscuous pregnane X receptor and less-promiscuous constitutive androstane receptor are crucial to initial ligand recognition, jump-starting the metabolic process. Other receptors, including farnesoid X receptor, vitamin D receptor, hepatocyte nuclear factor 4 alpha, peroxisome proliferator activated receptor, glucocorticoid receptor, liver X receptor, and RAR-related orphan receptor, are not directly linked to promiscuous xenobiotic binding, but clearly play important roles in the modulation of metabolic gene expression. Crystallographic studies of the ligand-binding domains of nine NRs involved in drug metabolism provide key insights into ligand-based and constitutive activity, coregulator recruitment, and gene regulation. Structures of other, noncanonical transcription factors also shed light on secondary, but important, pathways of control. Pharmacological targeting of some of these nuclear and atypical receptors has been instituted as a means to treat metabolic and developmental disorders and provides a future avenue to be explored for other members of the xenobiotic-sensing NRs.

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Analogues of Orphan Nuclear Receptor Small Heterodimer Partner Ligand and Apoptosis Inducer (E)-4-[3-(1-Adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic Acid. 2. Impact of 3-Chloro Group Replacement on Inhibition of Proliferation and Induction of Apoptosis of Leukemia and Cancer Cell Lines

Cited by 16 publications

References 44 publications

Exploring the nexus of nuclear receptors in hematological malignancies

Exploring the nexus of nuclear receptors in hematological malignancies

Cinnamic acid hybrids as anticancer agents: A mini‐review

Xenobiotic-sensing nuclear receptors involved in drug metabolism: a structural perspective

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