Suppression of Molecular Targets and Antiproliferative Effect of Citronellal on Triple-Negative Breast Cancer Cells

Fatima, Kaneez; Luqman, Suaib

doi:10.2174/1874467214666210309120626

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…ODC is a chief controller of cellular proliferation, and decreased apoptosis catalyzes ornithine conversion to polyamines. These polyamines are essential for modulators of ion transport channels, nucleic acid synthesis, DNA double-strand break repair pathway, and protein synthesis regulation (55). DHFR reduces dihydrofolic acid to tetrahydrofolic acid and helps in the biosynthesis of DNA bases responsible for cell proliferation (56).…”

Section: Discussionmentioning

confidence: 99%

Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities

2022

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Carvacrol, a monoterpene known for its pharmacological activities, is present in the essential oil of Origanum majorana, Origanum vulgare, Thymus vulgaris, and Lippia graveolens. It is used in food as a flavoring and preservative agent in cosmetics and medicines because of its useful bioactivities in clinical practice. However, carvacrol was not much explored for its anticancer potential. Targeting enzymes involved in carcinogenesis, such as ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2), lipoxygenase-5 (LOX-5), and hyaluronidase (HYAL) by monoterpenes are amongst the efficient approaches for cancer prevention and treatment. In this study, the efficacy of carvacrol was investigated against deregulated cancer biomarkers/targets in organ-specific human cancer cell lines (FaDu, K562, and A549) utilizing in vitro, in silico, and in vivo approaches. The efficacy of carvacrol was evaluated on human cancer cell lines using neutral red uptake (NRU), sulpho rhodamine B (SRB), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The mechanistic study was carried out in cell-based test systems. Further, the potency of carvacrol was confirmed by the quantitative real-time PCR analysis and molecular docking studies. The in vivo anti-tumor potential of carvacrol was performed on mice S-180 model, and the toxicity examination was accomplished through in silico approach. Carvacrol significantly impeded the growth of FaDu, K562, and A549 cell lines with IC50 values ranging from 9.61 ± 0.05 to 81.32 ± 11.83 μM. Further, the efficacy of carvacrol was explored against different cancer targets in FaDu, K562, and A549 cell lines. Carvacrol inhibits the ODC, COX-2, LOX-5, and HYAL activities in FaDu cell line and ODC, COX-2, and HYAL activities in K562 cell line. The results were validated by expression analysis revealing the downregulation of the targeted gene with a significant change in the transcript level of ODC and HYAL in FaDu cell line with a fold change of 1.56 and 1.61, respectively. A non-significant effect of carvacrol was observed on the downstream signaling pathway of PI3K and HIF-1α/vascular endothelial growth factor (VEGF) in FaDu cells. The cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and Annexin V-fluorescein isothiocyanate (FITC) experiments demonstrate that carvacrol induces apoptosis of FaDu cells. Further, the potency of carvacrol was also evaluated in vivo on mice S-180 tumor model, wherein it inhibits tumor growth (72%) at 75 mg/kg body weight (bw). ADMET studies predicted carvacrol as a safe molecule. Overall, carvacrol delayed the growth of FaDu, K562, and A549 cell lines by targeting enzymes involved in the carcinogenesis process. The existence of one hydroxyl group at the para position of carvacrol could be responsible for the anti-proliferative activity. Thus, carvacrol could be used as a pharmacophore to develop a safe and effective multi-targeted anti-cancer medicament.

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Section: Discussionmentioning

confidence: 99%

Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities

2022

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“…These mechanisms eventually trigger caspase‐9, which further stimulates caspase‐3 and ultimately leads to apoptosis. [ 47 ] The activated caspase 3 cleaves a variety of substrate proteins to effectively carry out apoptosis. [ 48 ] Our findings showed the augmented caspase‐3 and ‐9 activities in the U266 cells, which are treated with synthesized SCP‐Car‐NCs.…”

Section: Discussionmentioning

confidence: 99%

Anti‐cancer potential of selenium‐chitosan‐polyethylene glycol‐carvacrol nanocomposites in multiple myeloma U266 cells

Zhang

Zhao

Chinnathambi

et al. 2023

J Biochem & Molecular Tox

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Multiple myeloma (MM) is an incurable cancer that is characterized by malignant plasma cell proliferation. Approximately 10% of all blood cancers are MM, and there is no standard curative therapy. In this work, we intended to synthesize, characterize, and assess the anticancer effects of selenium/chitosan/polyethylene glycol–carvacrol nanocomposites (SCP‐Car‐NCs) on MM U266 cells in vitro. Various characterization techniques were used to characterize the synthesized SCP‐Car‐NCs. Several in vitro free radical scavenging experiments were conducted to test the ability of synthesized SCP‐Car‐NCs to scavenge the different free radicals. The cytotoxicity of SCP‐Car‐NCs was assessed on Vero and U266 cells using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay. By using various fluorescence staining techniques, the amount of reactive oxygen species (ROS) generation, MMP, and apoptosis were measured. Using commercial test kits, the levels of oxidative stress and apoptotic biomarkers in control and treated U266 cells were assessed. The highest peak in the UV spectral analysis was found to be at 271 nm, demonstrating the development of SCP‐Car‐NCs. Fourier transform infrared analysis showed that the synthesized SCP‐Car‐NCs contained a variety of stretching and bonding. The X‐ray diffraction study confirmed the crystallinity of SCP‐Car‐NCs. The dynamic light scattering analysis showed that the SCP‐Car‐NCs had an average size of 171 nm. The different free radicals, such as the 2,2‐diphenyl‐1‐picrylhydrazyl, hydroxyl, and peroxyl radicals, were significantly scavenged by the SCP‐Car‐NCs. According to the MTT assay results, the SCP‐Car‐NCs decreased the viability of U266 cells while having no impact on the proliferation of Vero cells. The SCP‐Car‐NCs significantly boosted ROS production, decreased the MMP level, and promoted apoptosis, as evidenced by the fluorescence staining experiments. In U266 cells treated with SCP‐Car‐NCs, the level of thiobarbituric acid reactive substances increased while superoxide dismutases and glutathione levels were reduced. In the SCP‐Car‐NCs treated U266 cells, it was found that the Bax, caspase‐3, and −9 activities had increased while the Bcl‐2 level had decreased. In conclusion, our findings show that SCP‐Car‐NCs treatment reduced the viability and increased apoptosis in the U266 cells, providing a new insight on SCP‐Car‐NCs' potential for usage in the future to treat MM.

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“…However, the cytotoxicity of these compounds on normal tissue is of concern as the IC 50 values of citronellol and citronellal were shown to be 1.96 and 1.81 nM respectively when tested against human monocyte derived macrophages. Independent antiproliferative studies of citronellal using Sulforhodamine B (SRB), MTT, and NRU (neutral red uptake) antiproliferative assays indicate its potential against a triple-negative breast cancer cell model (MDA-MB-231) [ 24 ]. The study also conducted in vitro experiments to evaluate citronellal’s activity against LOX-5 (arachidonate 5-lipoxygenase), finding the IC 50 value to be in the low micromolar range [ 24 ].…”

Section: Biological Activities Of Monoterpenesmentioning

confidence: 99%

“…Independent antiproliferative studies of citronellal using Sulforhodamine B (SRB), MTT, and NRU (neutral red uptake) antiproliferative assays indicate its potential against a triple-negative breast cancer cell model (MDA-MB-231) [ 24 ]. The study also conducted in vitro experiments to evaluate citronellal’s activity against LOX-5 (arachidonate 5-lipoxygenase), finding the IC 50 value to be in the low micromolar range [ 24 ]. Furthermore, the compounds efficacy was evaluated using the Ehrlich Ascites Carcinoma (EAC) model where it was found to inhibit tumor cell growth by 46% at 75 mg/kg, well below the lethal dose of 1000 mg/kg [ 25 ].…”

Section: Biological Activities Of Monoterpenesmentioning

confidence: 99%

Recent Advances in Chemistry and Antioxidant/Anticancer Biology of Monoterpene and Meroterpenoid Natural Product

Barras,

Ling,

Rivas

2024

Molecules

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Monoterpenes and meroterpenes are two large classes of isoprene-based molecules produced by terrestrial plants and unicellular organisms as diverse secondary metabolites. The global rising incidence of cancer has led to a renewed interest in natural products. These monoterpenes and meroterpenes represent a novel source of molecular scaffolds that can serve as medicinal chemistry platforms for the development of potential preclinical leads. Furthermore, some of these natural products are either abundant, or their synthetic strategies are scalable as it will be indicated here, facilitating their derivatization to expand their scope in drug discovery. This review is a collection of representative updates (from 2016–2023) in biologically active monoterpene and meroterpenoid natural products and focuses on the recent findings of the pharmacological potential of these bioactive compounds as well as the newly developed synthetic strategies employed to access them. Particular emphasis will be placed on the anticancer and antioxidant potential of these compounds in order to raise knowledge for further investigations into the development of potential anti-cancer therapeutics. The mounting experimental evidence from various research groups across the globe regarding the use of these natural products at pre-clinical levels, renders them a fast-track research area worth of attention.

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Suppression of Molecular Targets and Antiproliferative Effect of Citronellal on Triple-Negative Breast Cancer Cells

Cited by 7 publications

References 31 publications

Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities

Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities

Anti‐cancer potential of selenium‐chitosan‐polyethylene glycol‐carvacrol nanocomposites in multiple myeloma U266 cells

Recent Advances in Chemistry and Antioxidant/Anticancer Biology of Monoterpene and Meroterpenoid Natural Product

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