Neomenthol prevents the proliferation of skin cancer cells by restraining tubulin polymerization and hyaluronidase activity

Fatima, Kaneez; Masood, Nusrat; Wani, Zahoor A.; Meena, Abha; Luqman, Suaib

doi:10.1016/j.jare.2021.06.003

Cited by 21 publications

(14 citation statements)

References 66 publications

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“…DHFR reduces dihydrofolic acid to tetrahydrofolic acid and helps in the biosynthesis of DNA bases responsible for cell proliferation (56). COX-2 and LOX-5 accumulate at the inflammation sites produced in AA metabolism, an intermediate product of diacylglycerol (40). HYAL is a glycosylated protein cleaves at β-D 1-4 linkage of hyaluronan (HA) in the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Usually, it becomes active in lysosomes wherein pH is 3-3.5, but in cancer cells, it becomes active in the cytosol (58). The previous literature suggest unusual expression of selected targets enhanced the proliferation, invasion, angiogenesis, metastasis, and migration of the cancer cells at varied sites; therefore, these are considered significant cancer hallmarks (40).…”

Section: Discussionmentioning

confidence: 99%

“…The cell cycle analysis was carried out by the protocol reported by Fatima et al (40). The cell lines were fixed with 70% ethanol.…”

Section: Cell Cycle Analysis Dichloro-dihydro-fluorescein Diacetate M...mentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

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

2022

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“…Owing to its numerous biological properties, menthol is extensively used in multiple diseases, including inflammatory diseases (Du et al, 2020;Zhang et al, 2020), cancer (de Mesquita et al, 2019;Zielińska-Błajet et al, 2021), pain disorders (Hilfiger et al, 2021), respiratory disorders (Kanezaki et al, 2021), cardiovascular diseases (Silva, 2020), and skin diseases (Chrisman, 1978;Patel and Yosipovitch, 2010). Particularly, in vitro experiments have revealed the anti-proliferative potential of menthol against various tumor cell lines (Fatima et al, 2021). Mechanistically, menthol induces apoptosis in cancer cells, indicating its role as an anticancer agent (Beck et al, 2007) against a variety of cancers, such as prostate cancer (Kim et al, 2009), colon cancer (Faridi et al, 2016), skin cancer (Fatima et al, 2021), uveal melanoma (Walcher et al, 2018), pancreatic ductal Frontiers in Pharmacology frontiersin.org adenocarcinoma (Cucu et al, 2014), gastric cancer (Santo et al, 2021), liver cancer (Lin et al, 2001), leukemia (Lu et al, 2007a), and bladder cancer (Li et al, 2009) (Figure 2).…”

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confidence: 99%

Menthol: An underestimated anticancer agent

et al. 2023

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Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity via multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent.

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“…Graphical plotting of concentration vs. OD values was analyzed, and inhibition of proliferation by the extract was compared to vehicle-treated control. IC 50 values (concentration showing 50% proliferation inhibition) for carotenoid extract were calculated for both MCF-7 and MDA-MB-231 cells, and the extract was further evaluated in normal cells (HEK 293T) with corresponding IC 50 concentrations to check whether the anti-proliferative potency is restricted to cancer cell line only ( de Souza et al, 2021 ; Fatima et al, 2021 ; Kaur et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Anti-microbial, anti-oxidant, and anti-breast cancer properties unraveled in yeast carotenoids produced via cost-effective fermentation technique utilizing waste hydrolysate

Sinha

Das²,

Saha³

et al. 2023

Front. Microbiol.

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IntroductionNatural carotenoids are well known for their anti-oxidant property and also shown to have antimicrobial and anticancer efficacy. Production of carotenoids from microbial resources mainly from yeast has attracted commercial interest. Breast cancer has the highest incidence among women, and therapy resistance and lack of effective therapeutic strategies are major treatment bottlenecks, particularly for triple-negative subtypes. Yeast carotenoids are recently being evaluated for affordable, non-toxic, natural product-based therapies. In the present study, we have shown an environment-friendly and inexpensive method for carotenoid production from yeasts, utilizing “mandi” wastes, and investigated the biomedical properties of carotenoids, particularly antineoplastic properties.MethodsVegetable “mandi” waste was used to prepare waste hydrolysate, a culture medium, in which oleaginous red yeast Rhodosporidium sp. was grown. Carotenoid pigments were extracted using the solvent extraction method and analyzed by UV spectroscopy, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC). Antimicrobial, antioxidant, and anticancer activities of the extract were evaluated, followed by in silico docking and absorption, distribution, metabolism, and excretion/toxicity (ADME/T) studies.ResultsCarotenoid extract was found to be composed of three main pigments-β-carotene, torulene, and torularhodin. Extract exhibited significant antioxidant, antimicrobial, and anti-breast cancer activities in vitro while being biocompatible. Interestingly, carotenoids have shown better efficacy in triple-negative breast cancer (TNBC) cells than ER+PR+ cells. In silico evaluation predicted binding with breast cancer-specific molecular targets, specifically the three components showed good binding energy toward VEGF receptors and good drug likeliness properties, as well as less toxicity.DiscussionThis is the first report on anti-breast cancer activities, particularly targeting TNBC cells by red yeast carotenoids (β-carotene, torulene, and torularhodin) produced via a sustainable environment-friendly bioprocess utilizing waste hydrolysate.

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Neomenthol prevents the proliferation of skin cancer cells by restraining tubulin polymerization and hyaluronidase activity

Abstract: Graphical abstract

Cited by 21 publications

References 66 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

Menthol: An underestimated anticancer agent

Anti-microbial, anti-oxidant, and anti-breast cancer properties unraveled in yeast carotenoids produced via cost-effective fermentation technique utilizing waste hydrolysate

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