Estradiol 17β and Its Metabolites Stimulate Cell Proliferation and Antagonize Ascorbic Acid-Suppressed Cell Proliferation in Human Ovarian Cancer Cells

Li, Hui; Zhao, Yingjie; Li, Yan; Dai, Caifeng; Jobe, Sheikh O.; Yang, Xinggang; Li, Xing-Fu; Patankar, Manish S.; Magness, Ronald R.; Zheng, Jing

doi:10.1177/1933719113492211

Cited by 26 publications

(20 citation statements)

References 45 publications

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“…It is well recognized that MOE induces mitotic arrest and apoptosis in carcinoma cells [31]. However, in ovarian carcinoma cells lacking PRODH/POX [32], on the contrary, MOE stimulated cell proliferation [33]. The discrepancy may suggest that the underlying mechanism of this phenomenon could involve other factors than the proline availability and PRODH/POX activity.…”

Section: Discussionmentioning

confidence: 74%

Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX–Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model

Zaręba

Surażyński

Chruściel

et al. 2017

Cell Physiol Biochem

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Background/Aims: The effect of impaired intracellular proline availability for proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis was studied. Methods: We generated a constitutively knocked-down PRODH/POX MCF-7 breast cancer cell line (MCF-7^shPRODH/POX) as a model to analyze the functional consequences of impaired intracellular proline levels. We have used inhibitor of proline utilization in collagen biosynthesis, 2-metoxyestradiol (MOE), inhibitor of prolidase that generate proline, rapamycin (Rap) and glycyl-proline (GlyPro), substrate for prolidase. Collagen and DNA biosynthesis were evaluated by radiometric assays. Cell viability was determined using Nucleo-Counter NC-3000. The activity of prolidase was determined by colorimetric assay. Expression of proteins was assessed by Western blot and immunofluorescence bioimaging. Concentration of proline was analyzed by liquid chromatography with mass spectrometry. Results: PRODH/POX knockdown decreased DNA and collagen biosynthesis, whereas increased prolidase activity and intracellular proline level in MCF-7^shPRODH/POX cells. All studied compounds decreased cell viability in MCF-7 and MCF-7^shPRODH/POX cells. DNA biosynthesis was similarly inhibited by Rap and MOE in both cell lines, but GlyPro inhibited the process only in MCF-7^shPRODH/POX and MOE+GlyPro only in MCF-7 cells. All the compounds inhibited collagen biosynthesis, increased prolidase activity and cytoplasmic proline level in MCF-7^shPRODH/POX cells and contributed to the induction of pro-survival mode only in MCF-7^shPRODH/POX cells. In contrast, all studied compounds upregulated expression of pro-apoptotic protein only in MCF-7 cells. Conclusion: PRODH/POX was confirmed as a driver of apoptosis and proved the eligibility of MCF-7^shPRODH/POX cell line as a highly effective model to elucidate the different mechanisms underlying proline utilization or generation in PRODH/POX-dependent pro-apoptotic pathways.

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Section: Discussionmentioning

confidence: 74%

Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX–Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model

Zaręba

Surażyński

Chruściel

et al. 2017

Cell Physiol Biochem

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“…In contrast, ascorbic acid (AA), a naturally compound with antioxidant properties and one form of Vitamin C, has been implicated in preventing and treating cancers (22). The exact roles of estrogen and its active metabolites in the development of ovarian cancer is still controversial (1,23,24), the role of AA in cancer prevention and treatment is still not conclusive (23). In one of studies, Li et al examined the roles of estrogen and its active metabolites in the ovarian cancer progression (23).…”

Section: Sex Hormonesmentioning

confidence: 99%

“…In one of studies, Li et al examined the roles of estrogen and its active metabolites in the ovarian cancer progression (23). Li et al firstly found that the expression of cytochrome P450, family 1, subfamily A (CYP1A1) and B (CYP1B1), polypeptide 1, and catechol-O-methyltransferase (COMT), ERα, and ERβ in most cell lines tested including human ovarian surface epithelial (IOSE-385) and cancer cell lines (OVCAR-3, SKOV-3, and OVCA-432) (23). Active metabolites of estradiol 17 β (E2β, a steroid and estrogen sex hormone) including 2-hydroxyestradiol (2OHE2) (23).…”

Section: Sex Hormonesmentioning

confidence: 99%

“…Li et al firstly found that the expression of cytochrome P450, family 1, subfamily A (CYP1A1) and B (CYP1B1), polypeptide 1, and catechol-O-methyltransferase (COMT), ERα, and ERβ in most cell lines tested including human ovarian surface epithelial (IOSE-385) and cancer cell lines (OVCAR-3, SKOV-3, and OVCA-432) (23). Active metabolites of estradiol 17 β (E2β, a steroid and estrogen sex hormone) including 2-hydroxyestradiol (2OHE2) (23). They further found that treating those cells at physiological concentrations of E2β and its metabolites promoted proliferation of IOSE-385 and OVCAR-3 (23), and antagonist of ER suppressed E2β induced-proliferation of IOSE-385 and OVCAR-3, but not its metabolites induced proliferation of these two cell lines (23).…”

Section: Sex Hormonesmentioning

confidence: 99%

“…Active metabolites of estradiol 17 β (E2β, a steroid and estrogen sex hormone) including 2-hydroxyestradiol (2OHE2) (23). They further found that treating those cells at physiological concentrations of E2β and its metabolites promoted proliferation of IOSE-385 and OVCAR-3 (23), and antagonist of ER suppressed E2β induced-proliferation of IOSE-385 and OVCAR-3, but not its metabolites induced proliferation of these two cell lines (23). AA could suppress OVCAR-3 cell proliferation induced by serum, but its effects may be counteracted by E2β and its metabolites, suggesting that blockade of estrogen and its metabolites receptor may enhance AA inhibitory effects on growth of ovarian cancer (23).…”

Section: Sex Hormonesmentioning

confidence: 99%

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The possible pathology and pharmaceutical therapy of ovarian cancer

2016

Eur J Bio Med Res

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Human ovarian cancer is the most lethal gynecological cancer in the western world, causing enomous physical and mental suffering as well as financial hardship to the patients and their families. However, the etiology of the human ovarian cancer is not well understood. To date, multiple etiological factors, including but not limiting to Slit/Robo family, TGF-β family, sex hormones, and angiogenic factors, have been found involved in the pathological process of human ovarian cancer. The involvement of these factors in the human ovarian cancer makes them potential targets for treating human ovarian cancer. Given that human ovarian cancer is highly heterogeneous at both the cellular and molecular levels, the better understanding of actions of these factors and underlying cellular mechanisms in each subtype of human ovarian cancer cells will facilitate the personalized medicine of the lethal disease on the basis of individual characteristics at the cellular and molecular levels.

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Different mechanisms of action of 2, 2’, 4, 4’‐tetrabromodiphenyl ether (BDE‐47) and its metabolites (5‐OH‐BDE‐47 and 6‐OH‐BDE‐47) on cell proliferation in OVCAR‐3 ovarian cancer cells and MCF‐7 breast cancer cells

Karpeta

Maniecka

Gregoraszczuk

2016

J of Applied Toxicology

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Data concerning the possible action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent cancer are scarce. Some data showed that PBDEs may directly affect breast cancer cells formation and only one research showed increased proliferation of the OVCAR-3 cells, but the results are ambiguous and the mechanisms are not clear. There is growing evidence that not only parent compounds but also its metabolites may be involved in cancer development. The present study was, therefore, designed to determine the effect of BDE-47 and its metabolites (2.5 to 50 ng ml ) on proliferation (BrdU), cell-cycle genes (real-time PCR) and protein expression (Western blot), protein expression of oestrogen receptors (α β), extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase Cα (PKCα) in OVCAR-3 ovarian and MCF-7 breast cancer cells. In OVCAR-3 cells, the parent compound stimulated cell proliferation by activating CDK1, CDK7, E2F1 and E2F2. Independent of time of exposure, BDE-47 had no effect on ERα and ERβ protein expression and ERK1/2 and PKCα phosphorylation. Metabolites had no effect on cell proliferation but increased both ERs protein expression and ERK1/2 and PKCα phosphorylation. In MCF-7 cells, the parent compound displayed no effect on cell proliferation but decreased ERα and increased ERβ protein expression with concomitant induction of PKCα phosphorylation. Both metabolites increased MCF-7 cell proliferation, ERK1/2 and PKCα phosphorylation and decreased ERα and ERβ protein expression.We suggest that studies concerning PBDEs with fewer bromine atoms should be continued to understand environmental links to different hormone-dependent cancers. Copyright © 2016 John Wiley & Sons, Ltd.

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Estradiol 17β and Its Metabolites Stimulate Cell Proliferation and Antagonize Ascorbic Acid-Suppressed Cell Proliferation in Human Ovarian Cancer Cells

Cited by 26 publications

References 45 publications

Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX–Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model

Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX–Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model

The possible pathology and pharmaceutical therapy of ovarian cancer

Different mechanisms of action of 2, 2’, 4, 4’‐tetrabromodiphenyl ether (BDE‐47) and its metabolites (5‐OH‐BDE‐47 and 6‐OH‐BDE‐47) on cell proliferation in OVCAR‐3 ovarian cancer cells and MCF‐7 breast cancer cells

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