Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells

Ohno, Shuji; Shinoda, Satoshi; Toyoshima, Satoshi; Nakazawa, Hiroyuki; Makino, Tsunehisa; Nakajin, Shizuo

doi:10.1016/s0960-0760(02)00021-3

Cited by 125 publications

(87 citation statements)

References 31 publications

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“…Our results showed that treatment with dexamethasone had no effect on basal or TNF -induced apoptosis. Inhibition of cortisol synthesis by genistein, a strong suppressor of the steroidogenic enzymes steroid 21-hydroxylase and 3 -hydroxysteroid dehydrogenase in H295R cells , Ohno et al 2002, could not protect the cells from apoptosis. These results suggested that the enhancing effect of (Bu) 2 cAMP on TNF -induced apoptosis in H295R cells is not due to the increased secretion of cortisol into the culture medium.…”

Section: Discussionmentioning

confidence: 91%

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

Liu

Ora

et al. 2004

Journal of Molecular Endocrinology

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Adrenocorticotropin is the major regulator of adrenocortical development and function. It acts mainly through the cAMP-dependent protein kinase A (PKA) pathway. Our aim was to study the interaction of tumor necrosis factor-(TNF ) and the PKA pathway in adrenocortical cell proliferation and apoptosis. The PKA activator Dibutyryl cAMP ((Bu) 2 cAMP) strongly induced differentiation and inhibited proliferation in the human adrenocortical cell line NCI-H295R (H295R). TNF induced apoptosis of H295R cells. Interestingly, (Bu) 2 cAMP treatment clearly enhanced TNF -induced apoptosis in H295R cells, but not in another human adrenocortical cell line SW-13, the mouse adrenocortical Y-1 cell line or the human HeLa cell line. This synergistic effect was not due to the (Bu) 2 cAMP-induced glucocorticoid secretion since dexamethasone had no significant effect on the TNF -induced apoptosis. (Bu) 2 cAMP treatment rapidly increased the expression of the proto-oncogene c-myc in H295R cells, but not in SW-13, Y-1 or HeLa cells. In transient c-myc transfection assay, c-myc expression associated with decreased expression of the proliferation marker Ki-67 in H295R cells. In conclusion, cAMP-dependent protein kinase activation reduced proliferation and augmented TNF -induced apoptosis in adrenocortical H295R cells, and these effects were associated with increased c-myc expression.

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Section: Discussionmentioning

confidence: 91%

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

Liu

Ora

et al. 2004

Journal of Molecular Endocrinology

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“…Plant-flavonoids were shown to be potent aromatose inhibitors, a finding associated with increased intracellular cAMP concentrations. Ohno et al (118) further investigated the effects of plant flavonoids on cortisol production in H295R cells. Their results indicate that cells exposed to apigenin demonstrate decreased cortisol production and 3ß-HSD II and P450c21 activity.…”

Section: Apigenin and Leukemiamentioning

confidence: 99%

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Patel

Shukla²,

Gupta³

2007

Int J Oncol

296

362

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Abstract. Cancer is one of the major public health burdens in the United States and in other developed countries, causing approximately 7 million deaths every year worldwide. Cancer rates vary dramatically in different regions and populations around the globe, especially between developing and developed nations. Changes in cancer prevalence patterns occur within regions as their populations age or become progressively urbanized. Migration has also contributed to such variations as changes in dietary habits influence cancer rates. These epidemiologic findings strongly suggest that cancer rates are influenced by environmental factors including diet, which is largely preventable. Approaches to prevent cancer include overlapping strategies viz. chemoprevention or dietary cancer prevention. Chemoprevention aims at prevention or reversal of the initiation phase of carcinogenesis or arrest at progression of carcinogenesis through the administration of naturally occurring constituents or pharmacological agents. Cancer prevention through diet may be largely achievable by increased consumption of fruits and vegetables. Considerable attention has been devoted to identifying plant-derived dietary agents which could be developed as promising chemopreventives. One such agent is apigenin. A naturally occurring plant flavone (4', 5, 7,-trihydroxyflavone) abundantly present in common fruits and vegetables including parsley, onions, oranges, tea, chamomile, wheat sprouts and some seasonings. Apigenin has been shown to possess remarkable anti-inflammatory, antioxidant and anti-carcinogenic properties. In the last few years, significant progress has been made in studying the biological effects of apigenin at cellular and molecular levels. This review examines the cancer chemopreventive effects of apigenin in an organ-specificity format, evaluating its limitations and its considerable potential for development as a cancer chemopreventive agent.

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“…P450 scc, 450c17, P450c21, aromatase etc) (Gazdar et al 1990, Staels et al 1993. In recent years this cell line has been used as a model system to study the induction and inhibition of steroidogenic enzymes by a variety of compounds such as oestrogen (Gell et al 1998), phytoestrogens (Ohno et al 2002) and pesticides (Sanderson et al 2002). In these cells, oestrogen at high concentrations (1-10 µmol/l) inhibited cortisol synthesis by specifically inhibiting the activity of the 3 hydroxysteroid dehydrogenase enzyme (Gell et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Carboxy derivatives of isoflavones as affinity carriers for cytotoxic drug targeting in adrenocortical H295R carcinoma cells

Sömjen¹,

Stern²,

Knoll³

et al. 2003

Journal of Endocrinology

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Carboxy derivatives of isoflavones that exhibit oestrogenic/anti-oestrogenic properties were used as carriers for affinity drug targeting to H295R adrenocortical carcinoma cells that express transcripts of oestrogen receptor (ER) and . These derivatives were prepared by introducing a carboxymethyl group at the 6-position of genistein and of biochanin A, yielding 6CG and 6CB respectively. In transactivation assays, 6CG displayed mixed agonist/antagonist activity for ER , whereas 6CB displayed only weak antagonist activity. Low concentrations of oestrogen, 6CG and 6CB were capable of inducing proliferation in H295R cells and of stimulating creatine kinase (CK) specific activity, suggesting that these cells were sensitive to oestrogenic compounds. In in vivo experiments, both 6CG and 6CB were capable of inhibiting oestrogen-induced CK specific activity in rat tissues. For affinity drug targeting, the cytotoxic drug daunomycin was coupled to 6CB and 6CG, yielding 6CB-Dau and 6CG-Dau respectively. These conjugates were tested for their antiproliferative ability to inhibit DNA synthesis as assessed by incorporation of [ 3 H]thymidine in H295R cells. A dose-dependent cytoxicity was observed with both conjugates. At 0·3-3 nM, both conjugates were 10 to 30 times more potent than daunomycin. At 30 nM these conjugates were two to three times more potent than daunomycin. At concentrations ranging between 300 and 3000 nM, no difference in cytotoxicity was observed between the conjugates and daunomycin. When the cells were treated over a wide range of concentrations with a combination of 6CG plus daunomycin, the observed cytotoxicity was less than with daunomycin alone. When non-transformed rat enterocytes, which do not express ER, were treated with 6CG-Dau or daunomycin, the antiproliferative effect of 6CG-Dau was the same as that of daunomycin over the concentration range tested. These pilot studies suggest that the ready availability of oestrogenic binding sites in H295R cells can be exploited for site-directed chemotherapy.

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Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells

Cited by 125 publications

References 31 publications

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Carboxy derivatives of isoflavones as affinity carriers for cytotoxic drug targeting in adrenocortical H295R carcinoma cells

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