Metabolism of natural and synthetic steroids used in cancer treatment

Sandberg, Avery A.; Kirdani, Rashad Y.

doi:10.1016/0163-7258(88)90107-6

Cited by 3 publications

(2 citation statements)

References 167 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the significant partial antiandrogenic activity of 'progestins' such as CMA and MGA has not always been observed [15,16], possibly as a result of tissue or endpoint differences in androgen sensitivity. Other explanations for the divergent findings on the antiandrogenic effect of MGA, CMA, and MGA might pertain to in vivo metabolic conversion of these compounds [46], while 6-substituted, 17-OHP-derived synthetic 'progestins' appear to be metabolically stable in breast cancer cells in culture [47].…”

Section: Discussionmentioning

confidence: 94%

Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Poulin

Baker

Poirier

et al. 1991

Breast Cancer Res Tr

View full text Add to dashboard Cite

This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Discussionmentioning

confidence: 94%

Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Poulin

Baker

Poirier

et al. 1991

Breast Cancer Res Tr

View full text Add to dashboard Cite

show abstract

“…The results from [ 35 , 36 ] add considerable support for the statement that 5 α -androstan-16-one and similar compounds from aquatic macrophytes can serve as perspective anticancer agents which can inhibit proliferation of cancer cell lines. There are also the immediate and long-term prospects for use of these constitutes as agents against the resistant fungal strains, combined with systemic fungal infections [ 37 ].…”

Section: Resultsmentioning

confidence: 75%

Assessment of the Potential Biological Activity of Low Molecular Weight Metabolites of Freshwater Macrophytes with QSAR

et al. 2016

View full text Add to dashboard Cite

The paper focuses on the assessment of the spectrum of biological activities (antineoplastic, anti-inflammatory, antifungal, and antibacterial) with PASS (Prediction of Activity Spectra for Substances) for the major components of three macrophytes widespread in the Holarctic species of freshwater, emergent macrophyte with floating leaves, Nuphar lutea (L.) Sm., and two species of submergent macrophyte groups, Ceratophyllum demersum L. and Potamogeton obtusifolius (Mert. et Koch), for the discovery of their ecological and pharmacological potential. The predicted probability of anti-inflammatory or antineoplastic activities above 0.8 was observed for twenty compounds. The same compounds were also characterized by high probability of antifungal and antibacterial activity. Six metabolites, namely, hexanal, pentadecanal, tetradecanoic acid, dibutyl phthalate, hexadecanoic acid, and manool, were a part of the major components of all three studied plants, indicating their high ecological significance and a certain universalism in their use by various species of water plants for the implementation of ecological and biochemical functions. This report underlines the role of identified compounds not only as important components in regulation of biochemical and metabolic pathways and processes in aquatic ecological systems, but also as potential pharmacological agents in the fight against different diseases.

show abstract

The Role of Steroids in Cancer Treatment

Blickenstaff

1992

Antitumor Steriods

View full text Add to dashboard Cite

Metabolism of natural and synthetic steroids used in cancer treatment

Cited by 3 publications

References 167 publications

Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Assessment of the Potential Biological Activity of Low Molecular Weight Metabolites of Freshwater Macrophytes with QSAR

The Role of Steroids in Cancer Treatment

Contact Info

Product

Resources

About