Cirsilineol inhibits proliferation of lung squamous cell carcinoma by inducing ROS mediated apoptosis

Pathak, Gauri; Singh, Shilpi; Kumari, Priyanka; Hussain, Yusuf; Raza, Waseem; Luqman, Suaib; Meena, Abha

doi:10.1016/j.fct.2020.111550

Cited by 19 publications

(7 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, 5,3′-diOH Sin was verified to possess antiproliferative activities against human breast carcinoma cells, human leukemia cells, and human cervical cancer cells . 5,4′-diOH Sin also showed its potential in vitro regulatory effects on lung squamous cell carcinoma and various other cancer cell lines, although it was much less investigated than its isomer, 5,3′-diOH Sin. Based on the commonly accepted view, the bioactivities of parent compounds may be largely derived from their metabolites, so these two didemethylated PMFs could be partially responsible for the underlying biofunctions of 5-OH Sin.…”

Section: Resultsmentioning

confidence: 99%

Identification and Quantification of Both Methylation and Demethylation Biotransformation Metabolites of 5-Demethylsinensetin in Rats

Wang

Cao

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

5-Demethylated polymethoxyflavones (5-OH PMFs) are the most unique monodemethylated PMFs with relatively low polarities and are proved to possess better anticancer and anti-inflammatory effects than their respective permethoxylated ones. However, their detailed in vivo metabolic fates have not been fully studied. 5-Demethylsinensetin (5-OH Sin), being one of the 5demethylated citrus PMFs, was used in the present research to investigate its biotransformation in pharmacokinetics and excretion in rats. The results showed that 5-OH Sin was mostly accumulated in the large intestine, indicating its poor absorption in the small intestine. In addition, 5,3′-didemethylsinensetin and 5,4′-didemethylsinensetin were identified as two dominated metabolites of 5-OH Sin, and the C-3′ position of 5-OH Sin was more facile to be demethylated in systemic circulation. Moreover, other than demethylation reactions, the methylation transformation of 5-OH Sin and its metabolites were also observed and quantified, suggesting that the bidirectional biotransformation between 5-OH Sin and its parent compound, Sin, occurred under in vivo conditions.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification and Quantification of Both Methylation and Demethylation Biotransformation Metabolites of 5-Demethylsinensetin in Rats

Wang

Cao

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…Actaealactone, a type of neolignan found in the extracts of Actaea racemose, is reported to have antioxidant activity [ 62 ]. On the other hand, Cirsilineol, a flavone from Artemisia capillaris , has many medicinal properties such as anti-neoplastic activity [ 63 ], induction of ROS-mediated apoptosis [ 64 ], and inhibition of IFN-g signaling in a murine model [ 65 ]. The role of the compound Epigallocatechin 3-O-cinnamatein in different diseases, however, has not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches

Asseri¹,

Alam

Alzahrani³

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between −6.5 and −7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.

show abstract

“…Cirsilineol-4'-O-ß-D-glucopyranoside and cirsilineol were identified in EE. The toxicity risk analysis showed that cirsilineol possesses a mild risk for skin and ocular irritancy but is non-mutagenic (Pathak et al, 2020). In a previous study, Cirsilineol displayed anti-inflammatory effect through cyclooxygenase inhibitory activity (Kelm et al, 2000).…”

Section: The Developmental Toxicity Of Acteoside Cirsilineol-4'-o-ß-mentioning

confidence: 94%

Developmental toxicity of Clerodendrum cyrtophyllum turcz ethanol extract in zebrafish embryo

Nguyen

Quetin-Leclercq

et al. 2021

Journal of Ethnopharmacology

View full text Add to dashboard Cite

Clerodendrum cyrtophyllum Turcz has been used in traditional medicine for the treatment of various diseases. In spite of its therapeutic applications, research on its toxicity and teratogenicity is still limited. Aim of the study: The study aimed to investigate the developmental toxicity of the ethanol extract of C. cyrtophyllum (EE) in zebrafish embryo model. Material and methods: Major compounds from crude ethanol extract of Clerodendron cyrtophyllum Turcz leaves were determined using HPLC-DAD-Orbitrap-MS analysis. The developmental toxicity of EE were investigated using zebrafish embryo model. Zebrafish embryos at 6 h post-fertilization (hpf) were treated with EE at different concentrations. Egg coagulation, mortality, hatching, yolk sac edema, pericardial edema and teratogenicity were recorded each day for during a 5-day exposure. At time point 120 hpf, body length, pericardial area, heartbeat and yolk sac area were assessed. In order to elucidate molecular mechanisms for the developmental toxicity of EE, we further evaluated the effects of the EE on the expression of genes involved on signaling pathways affecting fish embryo's development such as heart development (gata5, myl7, myh6, has2, hand2, nkx 2.5), oxidative stress (cat, sod1, gpx4, gstp2), wnt pathway (β-catenin, wnt3a, wnt5, wnt8a, wnt11), or cell apoptosis (p53, bax, bcl2, casp3, casp8, casp9, apaf-1, gadd45bb) using qRT-PCR analysis. Results: Our results demonstrated that three major components including acteoside, cirsilineol and cirsilineol-4'-O-β-D-glucopyranoside were identified from EE. EE exposure during 6-96 h post-fertilization (hpf) at doses ranging from 80 to 200 μg/mL increased embryo mortality and reduced hatching rate. EE exposure at 20 and 40 μg/mL until 72-120 hpf induced a series of malformations, including yolk sac edema, pericardial edema, spine deformation, shorter body length. Based on two prediction models using a teratogenic index (TI), a 25% lethality concentration (LD25) and the no observed-adverse-effect level (NOAEL), EE is considered as teratogenic for zebrafish embryos with TI (LC50/EC50) and LD25/NOAEC values at 96 hpf reaching 3.87 and 15.73 respectively. The mRNA expression levels of p53, casp8, bax/bcl2, gstp2, nkx2.5, wnt3a, wnt11, gadd45bb and gata5 were significantly upregulated by EE exposure at 20 and 40 μg/mL while the expression of wnt5, hand2 and bcl2 were downregulated.

show abstract

Cirsilineol inhibits proliferation of lung squamous cell carcinoma by inducing ROS mediated apoptosis

Cited by 19 publications

References 50 publications

Identification and Quantification of Both Methylation and Demethylation Biotransformation Metabolites of 5-Demethylsinensetin in Rats

Identification and Quantification of Both Methylation and Demethylation Biotransformation Metabolites of 5-Demethylsinensetin in Rats

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches

Developmental toxicity of Clerodendrum cyrtophyllum turcz ethanol extract in zebrafish embryo

Contact Info

Product

Resources

About