The anticancer effects of 2-methoxyestradiol on human huh7 cells in vitro and in vivo

Hai, Tao; Mei, Juanjuan; Tang, Xiaoyan

doi:10.1016/j.bbrc.2019.02.068

Cited by 4 publications

(4 citation statements)

References 15 publications

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“…For example, 2-methoxyestradiol could induce apoptosis and arrest in the G2 phase of the cell cycle both against nasopharyngeal carcinoma [12] and human prostate cancer cell lines [13], inhibit the expression of caspase-3 [14], protect the brain from ischemic injury [15], and regulate the protein level of Bax or Bcl-2 [16]. Based on the published studies, 2-methoxyestradiol could inhibit the growth of different tumors cell lines [17][18][19], and the main model is breast cancer [20][21][22][23][24]. Furthermore, it has been indicated that 2-methoxyestradiol is selective to some specific cancer cell lines [9,11].…”

Section: -Methoxyestradiolmentioning

confidence: 99%

“…Their anti-tumor activities were evaluated to explore the structure-activity relationships of a series of derivatives from 2-methoxyestradiol. Based on the published studies, 2-methoxyestradiol could inhibit the growth of different tumors cell lines [17][18][19], and the main model is breast cancer [20][21][22][23][24]. Furthermore, it has been indicated that 2-methoxyestradiol is selective to some specific cancer cell lines [9,11].…”

Section: -Methoxyestradiolmentioning

confidence: 99%

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Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Sheng

Zhang

et al. 2020

Biomolecules

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In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 µM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 µM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; up regulation of Apaf-1, Bax, and cytochrome c; down regulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and -9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner.

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Section: -Methoxyestradiolmentioning

confidence: 99%

Section: -Methoxyestradiolmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Sheng

Zhang

et al. 2020

Biomolecules

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“…Acetylcholinesterase inhibition was weak in all extracts, but at 100 μg/mL, MC extracts from Dl, Gf, Ha, Pa, Es and Pm led to a ~ 50% inhibition (Figure 2B). Next, the cytotoxic potential of plant extracts was evaluated using the hepatocarcinoma Huh7 [48] and the ileocecal colorectal adenocarcinoma HCT-8 [49] cell lines. Overall, the HE and MC extracts were cytotoxic to the cell lines, suggesting an enrichment in cytotoxic metabolites.…”

Section: Resultsmentioning

confidence: 99%

Biochemical Analyses of Bioactive Extracts from Plants Native to Lampedusa, Sicily Minor Island

Lecce

Mérindol

Pérez

et al. 2022

Plants

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Major threats to the human lifespan include cancer, infectious diseases, diabetes, mental degenerative conditions and also reduced agricultural productivity due to climate changes, together with new and more devastating plant diseases. From all of this, the need arises to find new biopesticides and new medicines. Plants and microorganisms are the most important sources for isolating new metabolites. Lampedusa Island host a rich contingent of endemic species and subspecies. Seven plant species spontaneously growing in Lampedusa, i.e., Atriplex halimus L. (Ap), Daucus lopadusanus Tineo (Dl), Echinops spinosus Fiori (Es) Glaucium flavum Crantz (Gf) Hypericum aegypticum L: (Ha), Periploca angustifolia Labill (Pa), and Prasium majus L. (Pm) were collected, assessed for their metabolite content, and evaluated for potential applications in agriculture and medicine. The HPLC-MS analysis of n-hexane (HE) and CH2Cl2 (MC) extracts and the residual aqueous phases (WR) showed the presence of several metabolites in both organic extracts. Crude HE and MC extracts from Dl and He significantly inhibited butyrylcholinesterase, as did WR from the extraction of Dl and Pa. HE and MC extracts showed a significant toxicity towards hepatocarcinoma Huh7, while Dl, Ha and Er HE extracts were the most potently cytotoxic to ileocecal colorectal adenocarcinoma HCT-8 cell lines. Most extracts showed antiviral activity. At the lowest concentration tested (1.56 μg/mL), Dl, Gf and Ap MC extracts inhibited betacoronavirus HCoV-OC43 infection by> 2 fold, while the n-hexane extract of Pm was the most potent. In addition, at 1.56 μg/mL, potent inhibition (>10 fold) of dengue virus was detected for Dl, Er, and Pm HE extracts, while Pa and Ap MC extracts dampened infections to undetectable levels. Regarding to phytotoxicity, MC extracts from Er, Ap and Pm were more effective in inhibiting tomato rootlet elongation; the same first two extracts also inhibited seed cress germination while its radicle elongation, due to high sensitivity, was affected by all the extracts. Es and Gf MC extracts also inhibited seed germination of Phelipanche ramosa. Thus, we have uncovered that many of these Lampedusa plants displayed promising biopesticide, antiviral, and biological properties.

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“…Up to this date, there is no data about the induction of Parkinson-like symptoms in animals by 2-ME2. Several canine cancer cell lines [ 17 ], as well as tumor xenograft development nude mice, have been used to research 2-ME2’s anticancer features [ 18 , 19 ]. In this project, the inverse relationship between PD and cancer incidence has specifically drawn the researchers’ attention.…”

Section: Introductionmentioning

confidence: 99%

2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson’s Disease

Bastian,

Konieczna,

Dulski

et al. 2023

Mol Neurobiol

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Estrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Methoxestradiol (2-ME2), a 17β-estradiol (E2) metabolite, is known for its anticancer effects as observed both in vivo and in vitro. 2-ME2 affects all actively dividing cells, including neurons. The study aimed to determine whether 2-ME2 is a potentially cancer-protective or rather neurodegenerative agent in a specific tissue culture model as well as a clinical setup. In this study, 2-ME2 activity was determined in a Parkinson’s disease (PD) in vitro model based on the neuroblastoma SH-SY5Y cell line. The obtained results suggest that 2-ME2 generates nitro-oxidative stress and controls heat shock proteins (HSP), resulting in DNA strand breakage and apoptosis. On the one hand, it may affect intensely dividing cells preventing cancer development; however, on the other hand, this kind of activity within the central nervous system may promote neurodegenerative diseases like PD. Thus, the translational value of 2-ME2’s neurotoxic activity in a PD in vitro model was also investigated. LC–MS/MS technique was used to evaluate estrogens and their derivatives, namely, hydroxy and methoxyestrogens, in PD patients’ blood, whereas the stopped-flow method was used to assess hydrogen peroxide (H2O2) levels. Methoxyestrogens and H2O2 levels were increased in patients’ blood as compared to control subjects, but hydoxyestrogens were simultaneously decreased. From the above, we suggest that the determination of plasma levels of methoxyestrogens and H2O2 may be a novel PD biomarker. The presented research is the subject of the pending patent application “The use of hydrogen peroxide and 17β-estradiol and its metabolites as biomarkers in the diagnosis of neurodegenerative diseases,” no. P.441360.

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The anticancer effects of 2-methoxyestradiol on human huh7 cells in vitro and in vivo

Cited by 4 publications

References 15 publications

Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Biochemical Analyses of Bioactive Extracts from Plants Native to Lampedusa, Sicily Minor Island

2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson’s Disease

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