关键词: AA, Arachidonic acid AKLP, Alkaline phosphatase Ab/Am, Antibiotic/antimycotic BE, Binding energy BIL, Bilirubin total & direct BSA, Bovine serum albumin BUN, Blood urea nitrogen CATD, Cathepsin D CHOL, Cholesterol CM-H2DCFDA, Chloromethyl derivative of dichloro fluorescin diacetate COX-2, Cyclooxygenase 2 CRTN, Creatinine Cancer biomarker DCFDA, 2′,7′ dichloro fluorescin diacetate DFMO, α-difluoro methyl ornithine DHFR, Dihydrofolatereductase DMEM, Dulbecco’s minimal essential media DMSO, Dimethyl sulfoxide DNA, Deoxyribonucleic acid DOXO, Doxorubicin EAC, Ehlrich Ascites Carcinoma EC50, Half maximal effective concentration EDTA, Ethylene diamine tetra acetic acid ELISA, enzyme-linked immunosorbent assay Ehrlich Ascites Carcinoma FACS, Fluorescence-Activated Cell Sorting FBS, Fetal bovine serum FDA, Food and Drug Administration FOX, Ferrous oxidation-xylenol orange GAPDH, Glyceraldehyde 3-phosphate dehydrogenase, HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid HA, Hyaluronic acid HDAC, Histone deacetylase HDL, High density lipoprotein HYAL, Hyaluronidase Human epidermoid carcinoma Hyaluronidase IC50, Half maximal inhibitory concentration IDT, Integrated DNA Technologies Ki, Inhibitory constant LDH, Lactate dehydrogenase LOX-5, Lipoxygenase-5 MEF, Mean erythrocyte fragility MMP, Mitochondrial membrane potential MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTX, Methotrexate NAC, N-acetyl cysteine NADPH, Nicotinamide adenine dinucleotide phosphate hydrogen NRU, Neutral red uptake NaOH, Sodium hydroxide Neomenthol ODC, Ornithine decarboxylase OECD, Organization for Economic Co-operation and Development OF, Osmotic fragility PBS, Phosphate buffer saline PCR, Polymerase chain reaction PDB, Protein Data Bank PDT, Podophyllotoxin PEP A, pepstatin A PI, Propidium iodide PI3K, Phosphotidyl inositol-3 kinase PKB/Akt, Protein kinase B RBC, Red blood cell RIPA, Radio immune precipitation assay buffer RNA, Ribonucleic acid RNase A, Ribonuclease A ROS, Reactive oxygen species RPMI, Roswell park memorial institute Rh123, Rhodamine 123 SGOT, Aspartate aminotransferase SGPT, Alanine aminotransferase SRB, Sulphorhodamine B TCA, Tricarboxylic acid TMPD, N,N,N′,N′-tetramethyl-p-phenylenediamine TNBS, Trinitrobenzenesulphonic acid TPA, 12-O-Tetradecanoylphorbol-13-acetate TPR, Total protein TRIG, Triglyceraldehyde TRPM8, Transient receptor potential member 8 Tubulin URIC, Uric acid WBC, White blood cell mTOR, Mammalian target of rapamycin

Mesh : Animals Cell Proliferation HEK293 Cells Humans Hyaluronoglucosaminidase Mice Molecular Docking Simulation Polymerization Skin Neoplasms / drug therapy Tubulin

来  源:   DOI:10.1016/j.jare.2021.06.003   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment.
To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines.
The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico, ex vivo and in vivo approaches.
Neomenthol exhibits a promising activity (IC50 17.3 ± 6.49 μM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC50 12.81 ± 0.01 μM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies.
Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis.
摘要:
新薄荷醇,一种环状单萜,是薄荷醇的立体异构体,存在于薄荷醇的精油中。它在食品中用作调味剂,在化妆品和药品,因为它的冷却效果。然而,新薄荷脑对其抗癌潜力的研究并不多。此外,靶向透明质酸酶,组织蛋白酶-D,植物化学物质和ODC是癌症预防和/或治疗的有效方法之一。
研究新薄荷脑对人类癌症的分子和细胞靶标的抗增殖潜力(A431,PC-3,K562,A549,FaDu,MDA-MB-231,COLO-205,MCF-7和WRL-68)和正常(HEK-293)细胞系。
使用SRB在人类癌症和正常细胞系上评估了新薄荷脑的效力,NRU和MTT测定。在无细胞和基于细胞的测试系统中进行了新薄荷醇的基于分子靶标的研究。Further,通过实时定量PCR分析和分子对接研究证实了新薄荷脑的效力.在小鼠EAC模型上进行了新薄荷脑的体内抗癌潜力,并通过计算机模拟进行了毒性检查。离体和体内方法。
新薄荷醇通过阻止G2/M期并增加亚二倍体细胞的数量,对人表皮样癌(A431)细胞具有有希望的活性(IC5017.3±6.49μM)。它显着抑制透明质酸酶活性(IC5012.81±0.01μM)并影响微管蛋白聚合。表达分析和分子对接研究支持基于体外分子和细胞靶标的结果。新薄荷醇在75mg/kgbw时可预防EAC肿瘤形成58.84%,并抑制透明质酸酶活性高达10%,腹膜内剂量。在急性口服毒性研究中发现1000毫克/千克体重的口服剂量是安全的。
新薄荷醇通过抑制微管蛋白聚合和透明质酸酶活性来延缓皮肤癌细胞的生长,负责肿瘤的生长,转移,和血管生成。
公众号