Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Dec. 12, 2023

Abstract Colorectal neoplasms are one of the deadliest diseases among all cancers worldwide. Thymoquinone (TQ) is a natural compound Nigella sativa that has been used in traditional medicine against variety acute/chronic such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders. This review aims to present detailed report on studies conducted anti-cancer properties TQ colorectal cancer, both vitro vivo. stands promising therapeutic agent can enhance efficacy existing cancer treatments while minimizing associated adverse effects. The combination with other anti-neoplastic agents promoted treatments. Further research needed acquire more comprehensive understanding its exact molecular targets pathways maximize clinical usefulness. These investigations may potentially aid development novel techniques combat drug resistance surmount obstacles presented by chemotherapy radiotherapy. Graphical

Language: Английский

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The Prognostic and Therapeutic Implications of the Chemoresistance Gene BIRC5 in Triple-Negative Breast Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(21), P. 5180 - 5180

Published: Oct. 22, 2022

Chemoresistance affects TNBC patient treatment responses. Therefore, identifying the chemoresistant gene provides a new approach to understanding chemoresistance in TNBC. BIRC5 was examined current study as tool for predicting prognosis of patients and assisting developing alternative therapies using online database tools. According studies, highly expressed 45 90% patients. is not only abundantly but also contributes resistance chemotherapy, anti-HER2 therapy, radiotherapy. Patients with increased expression had median survival 31.2 months compared 85.8 low-expression counterparts (HR, 1.73; CI, 1.4−2.13; p = 2.5 × 10−7). The overall survival, disease-free relapse-free distant metastasis-free complete pathological response high who received any chemotherapy (Taxane, Ixabepilone, FAC, CMF, FEC, Anthracycline) therapy (Trastuzumab, Lapatinib) did differ significantly from those receiving other treatment. Data obtained indicate that promoter region substantially methylated, hypermethylation associated higher mRNA (p < 0.05). findings this outline role chemotherapy-induced TNBC, further indicating may serve promising prognostic biomarker could be possible therapeutic target. Meanwhile, several vitro studies show flavonoids were effective inhibiting genetically diverse cells. would strategy preventing treating molecule.

Language: Английский

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Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell‐Death in MDA‐MB‐231 Cell Line

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 20, 2025

ABSTRACT Arginase plays a crucial role in the urea cycle; it also has immunosuppressive and pro‐tumor effects. The present study aimed to assess effects of arginase inhibition by thymoquinone (2‐Isopropyl‐5‐methyl‐1,4‐benzoquinone), an active compound Nigella sativa , on cell death MDA‐MB‐231 triple‐negative breast tumor line. Cell viability assays, Western blot analysis, flow cytometry analysis were used characterize oxidative stress death. Our results showed that activity with significantly increased intracellular nitric oxide levels resulted overproduction cellular mitochondrial reactive oxygen species. Reductions viability, cycle arrest, observed. Loss transmembrane potential, activation caspase‐3, ‐7, ‐9, cleavage PARP, condensation and/or fragmentation nuclei, suggest this involved apoptosis. Furthermore, cytoplasm vacuole formation increase ratio [LC3‐II/LC3‐I] suggests concomitant autophagy Altogether, highlighted induces hybrid type defined as oxiapoptophagy. Thus, line could be, part, anticancer effect thymoquinone.

Language: Английский

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TQFL19, a Novel Derivative of Thymoquinone (TQ), Plays an Essential Role by Inhibiting Cell Growth, Metastasis, and Invasion in Triple-Negative Breast Cancer

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 773 - 773

Published: Feb. 7, 2025

Breast cancer (BC) is a significant public health concern globally. Triple-negative breast (TNBC) considered the most challenging type, as it defined by an absence of estrogen and progesterone receptor expression, along with lack HER2 overexpression. In current study, we developed novel thymoquinone (TQ), TQFL19, to control TNBC progression. Purpose: The study aimed investigate anticancer potential newly synthesized TQFL19 against TNBC. Study design: To achieve our research goals, meticulously both in vitro vivo studies focused on cell growth, metastasis, invasion. Results: Characterization ADMET properties prediction were first performed before treating cells. exhibited more potent cytotoxicity than TQ 4T1, BT-549, MDA-MB-231 cells induced apoptosis 4T1 MDA-MB-231, besides cycle arrest MDA-MB-231. mice allograft revealed ability hinder migration, metastasis Conclusions: results suggest that potentially inhibited conclude could be viable candidate for therapy.

Language: Английский

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Promotion of Autophagy and Apoptosis in Colorectal Cancer Exposed to Imatinib and Thymoquinone

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(4)

Published: March 27, 2025

Cancer cells possess high proliferative ability and usually override apoptosis metastasize to distant lesions. Autophagy in cancer is a double-edged weapon where cross-regulation postulation between autophagy exists. The aim of the present study was investigate effect adding Thymoquinone (TQ) Imatinib (IM) HCT116 human colorectal cell line model on various apoptotic markers. combination doses IM TQ were selected according our previous concerned with cytotoxicity uptake/efflux genes modulation. In current study, induced which turn enhanced apoptosis. Moreover, early evidenced. induction both resulted programmed death. assessment AMPK, Par-4, markers, colony formation assays, flow cytometry detection by acridine orange proved this rapport.

Language: Английский

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Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells

Nutrients, Journal Year: 2022, Volume and Issue: 14(22), P. 4787 - 4787

Published: Nov. 13, 2022

The variety of therapies available for treating and preventing triple-negative breast cancer (TNBC) is constrained by the absence progesterone receptors, estrogen human epidermal growth factor receptor 2. Nrf2 (nuclear factor-erythroid 2-related factor), PD-L1 (program cell death ligand 1), a downstream signaling target, have strong correlation to oxidative stress inflammation, major factors in development progression TNBC. In this study, genetically distinct MDA-MB-231 MDA-MB-468 TNBC cells were treated with natural component thymoquinone (TQ). results show that TQ exhibits considerable antioxidant activity decreases generation H2O2, at same time increasing catalase (CAT) activity, superoxide dismutase (SOD) enzyme, glutathione (GSH). Additionally, treatment increased levels different genes involved stress-antioxidant defense system PRNP, NQO1, GCLM both lines significant large-fold change (+157.65 vs. +1.7, +48.87 +2.63 +4.78 +2.17), respectively. mRNA protein expression also significantly TQ-treated despite being higher (6.67 4.06). Meanwhile, administration while decreasing lines. conclusion, modifies multiple oxidative-stress-antioxidant genes, ROS, enzymes, Nrf2, protein, pointing therapeutic potential chemopreventive utilization

Language: Английский

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Identifying synergistic combinations of Doxorubicin-Loaded polyquercetin nanoparticles and natural Products: Implications for breast cancer therapy

International Journal of Pharmaceutics, Journal Year: 2023, Volume and Issue: 645, P. 123392 - 123392

Published: Sept. 6, 2023

Language: Английский

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The Role of Apoptotic Genes and Protein-Protein Interactions in Triple-negative Breast Cancer

Cancer Genomics & Proteomics, Journal Year: 2023, Volume and Issue: 20(3), P. 247 - 272

Published: Jan. 1, 2023

Abstract

Background/Aim: Compared to other breast cancer types, triple-negative (TNBC) has historically had few treatment alternatives. Therefore, exploring and pinpointing potentially implicated genes could be used for treating managing TNBC. By doing this, we will provide essential data comprehend how the are involved in apoptotic pathways of cells identify potential therapeutic targets. Analysis a single genetic alteration may not reveal pathogenicity driving TNBC due high genomic complexity heterogeneity searching through large variety gene interactions enabled identification molecular genes. Materials Methods: This study integrated bioinformatics methods such as UALCAN, TNM plotter, PANTHER, GO-KEEG PPIs assess expression, protein-protein interaction (PPI), transcription factor apoptosis-regulated Results: normal tissue, expressions BNIP3, TNFRSF10B, MCL1, CASP4 were downregulated UALCAN. At same time, BIK, AKT1, BAD, FADD, DIABLO, CASP9 was down-regulated bc-GeneExMiner v4.5 mRNA expression (BCGM) databases. Based on GO term enrichment analysis, cellular process (GO:0009987), which about 21 genes, is top category biological processes (BP), followed by regulation (GO:0065007). We identified 29 differentially regulated pathways, including p53 pathway, angiogenesis, apoptosis signaling Alzheimer's disease presenilin pathway. examined between that regulate apoptosis; CASP3 interact with TNF, TNFRSRF10A, TNFRSF10; additionally, significantly forms CASP9, DFFA, TP53, DIABLO. In 10 factors, androgen receptor (AR) interacts five (p<0.0001; q<0.01), retinoic acid alpha (RARA) q<0.01) ring finger protein (RNF2) q<0.01). Overall, profile, PPIs, apoptosis-TF findings suggest 27 might promising targets Furthermore, from total key CASP2, CASP3, DAPK1, TRAF2, TRAF3 correlated poor overall survival (p-value <0.05); they play important roles progression attractive offer new candidate molecules targeted therapy. Conclusion: Our demonstrate substantially associated rate (OS) difference patients out specific this study, crucial development interventions.

Language: Английский

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Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9878 - 9878

Published: June 8, 2023

The lack of identifiable molecular targets or biomarkers hinders the development treatment options in triple-negative breast cancer (TNBC). However, natural products offer a promising alternative by targeting inflammatory chemokines tumor microenvironment (TME). Chemokines are crucial promoting growth and metastasis correlate to altered process. In present study, we evaluated anti-inflammatory antimetastatic effects product thymoquinone (TQ) on TNF-α-stimulated TNBC cells (MDA-MB-231 MDA-MB-468) study cytotoxic, antiproliferative, anticolony, antimigratory, antichemokine using enzyme-linked immunosorbent assays, quantitative real-time reverse transcription-polymerase chain reactions, Western blots were used sequence validate microarray results further. Four downregulated cytokines identified, CCL2 CCL20 MDA-MB-468 CCL3 CCL4 MDA-MB-231 cells. Furthermore, when compared with cells, two sensitive TQ's effect preventing cell migration. It was concluded from this investigation that genetically different lines may respond TQ differently, as Therefore, indicate be recommended component therapeutic strategy for treatment. These outcomes stem compound's capacity suppress chemokine. Even though these findings support usage part therapy associated identified chemokine dysregulations, additional vivo studies needed confirm vitro results.

Language: Английский

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Decreased Autophagic Activity in Triple-Negative Breast Cancer Cells upon Hydroxychloroquine and Thymoquinone Combination Treatment

Hitit Medical Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Objective: Autophagy plays a significant role in breast cancer tumorigenesis, including triple-negative cancer. Research indicates that hydroxychloroquine and thymoquinone modulate autophagy, potentially suppressing its activity. However, their combined effects on autophagy remain unexplored. In this study, we investigated the potential anti-cancer autophagy-modulating of hydroxychloroquine-thymoquinone combination cells vitro. Material Method: The viability MDA-MB-231 was evaluated after treatment with (10-210 µM) (5-45 for 24 48 hours using WST-1 assay. Combination were analyzed Chou-Talalay method CompuSyn (v.10). Autophagic vesicles visualized an Detection Kit fluorescence microscopy to investigate decrease cell viability. Statistical analysis performed GraphPad Prism (v.8.3.0). Results: At both 24- 48-hour intervals post-treatment, observed treatments individually (p1). hours, favorable dose reduction evident (dose index >1), while results showed unfavorable

Language: Английский

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