Progesterone Interacts with P-Glycoprotein in Multidrug-resistant Cells and in the Endometrium of Gravid Uterus

Yang, Chia-Ping Huang; Depinho, S. G.; Greenberger, Lee M.; Arceci, Robert J.; Horwitz, Susan Band

doi:10.1016/s0021-9258(19)85010-x

Cited by 249 publications

(35 citation statements)

References 30 publications

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“…Furthermore, modulation of ABCB1 function can occur indirectly by altering expression or directly by inhibiting efflux. It is believed that because of the extreme lipophilic nature of progesterone, progesterone has the ability to bind to but not to be released from ABCB1, thus competitively inhibiting its function, 23 although the basis for this inhibition is not fully understood. 42 Given that transplacental transfer was not altered with progesterone treatment, progesterone does not appear to exhibit either direct or indirect control of placental ABCB1 function.…”

Section: Discussionmentioning

confidence: 99%

“…Information concerning the physiological regulation of placental ABCB1 is extremely limited.We have previously shown a positive correlation between maternal plasma progesterone levels and the expression of placental Abcb1b, suggesting a potential regulatory role of progesterone on ABCB1 expression. 18 Studies of ABCB1 regulation in other tissues 21,22 and cell lines [23][24][25] indicate that Abcb1b specifically may be positively regulated by progesterone. However, whether physiological levels of progesterone are sufficient to alter placental ABCB1 expression remains to be determined.…”

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confidence: 99%

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Functional Changes of Mouse Placental Multidrug Resistance Phosphoglycoprotein (ABCB1) With Advancing Gestation and Regulation by Progesterone

et al. 2007

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Multidrug resistance phosphoglycoprotein (ABCB1) has been shown to limit maternal-fetal transfer by actively excluding ABCB1 substrates. The authors have previously demonstrated a marked decrease in placental ABCB1 expression in the human and mouse with advancing gestation. In the present study, it is hypothesized that the decrease in ABCB1 expression will result in increased transplacental transfer of ABCB1 substrates over the second half of gestation and that progesterone exhibits a regulatory role on placental ABCB1 expression and function. The authors demonstrate a significant increase in transplacental transfer of [(3)H]digoxin (an ABCB1 substrate) in late gestation (E18.5; P < .001) when compared to earlier embryonic days. Furthermore, maternal plasma progesterone levels did not influence expression or function of ABCB1. The authors conclude that the fetus is increasingly exposed to both endogenous and exogenous substrates of ABCB1 present in the maternal circulation with advancing gestation and that progesterone does not elicit a regulatory role on placental ABCB1 expression or function in vivo.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Functional Changes of Mouse Placental Multidrug Resistance Phosphoglycoprotein (ABCB1) With Advancing Gestation and Regulation by Progesterone

et al. 2007

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“…Extensive studies carried out with verapamil and cyclosporins to investigate their ability to overcome MDR showed that cyclosporin A reversed P-glycoprotein-mediated multi drug resistance as efficiently as other prototype compounds of resistance modifiers [81][82][83][84]. Pregnane derivatives and other steroidal compounds and antiestrogenic drugs increased the sensitivity of MDR cells to anticancer drugs [85][86][87].…”

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confidence: 99%

Pregnane Glycosides

Panda

Banerjee

Mandal

et al. 2006

Natural Product Communications

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Pregnane glycosides constitute a class of compounds widely distributed in the plant kingdom. Many of them have shown either anticarcinogenic or cancer inhibitory properties, besides other useful biological activities. New chromatographic techniques and advances in spectroscopic and spectrometric methods have accelerated the purification and structure determination of novel glycosides of this series. A compilation of the pregnane glycosides isolated from 1995 until the middle of 2005, along with their physical data, structures and occurrence are presented in this review, which also summarizes, with suitable examples, recent developments in isolation and purification techniques, and structural elucidation using modern spectrometric methods like ESIMS and tandem mass spectrometry, and 2D NMR spectroscopic strategies. The reported anticancer and other biological activities of pregnane glycosides are also discussed.

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“…The first mention of progesterone as an MDR regulator was published in 1989 by Yang [ 65 ]. Many studies have been devoted to progesterone and its analogs as modulators of P-gp mediated resistance of tumor cells [ 66 , 67 , 68 , 69 ].…”

Section: Progestins As Chemosensitizers Possible Targetsmentioning

confidence: 99%

Progestins as Anticancer Drugs and Chemosensitizers, New Targets and Applications

Федотчева

Shimanovsky

2021

Pharmaceutics

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Progesterone and its synthetic analogues, progestins, participate in the regulation of cell differentiation, proliferation and cell cycle progression. Progestins are usually applied for contraception, maintenance of pregnancy, and hormone replacement therapy. Recently, their effectiveness in the treatment of hormone-sensitive tumors was revealed. According to current data, the anticancer activity of progestins is mainly mediated by their cytotoxic and chemosensitizing influence on different cancer cells. In connection with the detection of previously unknown targets of the progestin action, which include the membrane-associated progesterone receptor (PR), non-specific transporters related to the multidrug resistance (MDR) and mitochondrial permeability transition pore (MPTP), and checkpoints of different signaling pathways, new aspects of their application have emerged. It is likely that the favorable influence of progestins is predominantly associated with the modulation of expression and activity of MDR-related proteins,the inhibition of survival signaling pathways, especially TGF-β and Wnt/β-catenin pathways, which activate the proliferation and promote MDR in cancer cells, and the facilitation of mitochondrial-dependent apoptosis. Biological effects of progestins are mediated by the inhibition of these signaling pathways, as well as the direct interaction with the nucleotide-binding domain of ABC-transporters and mitochondrial adenylate translocase as an MPTP component. In these ways, progestins can restore the proliferative balance, the ability for apoptosis, and chemosensitivity to drugs, which is especially important for hormone-dependent tumors associated with estrogen stress, epithelial-to-mesenchymal transition, and drug resistance.

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Progesterone Interacts with P-Glycoprotein in Multidrug-resistant Cells and in the Endometrium of Gravid Uterus

Cited by 249 publications

References 30 publications

Functional Changes of Mouse Placental Multidrug Resistance Phosphoglycoprotein (ABCB1) With Advancing Gestation and Regulation by Progesterone

Functional Changes of Mouse Placental Multidrug Resistance Phosphoglycoprotein (ABCB1) With Advancing Gestation and Regulation by Progesterone

Pregnane Glycosides

Progestins as Anticancer Drugs and Chemosensitizers, New Targets and Applications

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