Cryptotanshinone Regulates Androgen Synthesis through the ERK/c‐Fos/CYP17 Pathway in Porcine Granulosa Cells

Ye, Danfeng; Li, Meifang; Zhang, Yuehui; Wang, Xinhua; Liu, Hua; Wu, Wanting; Ma, Wan-ying; Quan, Kewei; Ng, Ernest Hung-Yu; Wu, Xiaoke; Lai, Ming-Kuen; Ma, Hongxia

doi:10.1155/2017/5985703

Cited by 9 publications

(4 citation statements)

References 44 publications

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“…Polycystic ovary syndrome (PCOS) is a common and disturbing endocrine disorder that affects approximately 7% of reproductive-aged women and is characterized by hyperandrogenism, ovulatory dysfunction, insulin resistance, polycystic ovarian morphology on ultrasound, weight gain, hirsutism, and other virilizing signs; hyperandrogenism is the main feature of PCOS [ 1 , 2 , 3 , 4 ]. According to previous reports, conditions of hyperandrogenic ovaries as well as adrenal androgen secretion appear to be upregulated in PCOS [ 2 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model

et al. 2018

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Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

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Section: Introductionmentioning

confidence: 99%

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model

et al. 2018

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“…Furthermore, we detected potential regulatory mechanisms of CREBZF in apoptosis induction in ovarian granulosa cells. ERK1/2 activate cell cycle progression, mediate the mitogenic action of hormones and growth factors, stimulate ovarian cell proliferation, differentiation, and secretion activity [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], and suppress cell apoptosis [ 39 , 40 , 41 , 42 ]. The ERK1/2 signaling pathway is regulated in the ovary [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of CREBZF Increases Cell Apoptosis in Mouse Ovarian Granulosa Cells by Regulating the ERK1/2 and mTOR Signaling Pathways

Chen

Wen

Lin

et al. 2018

IJMS

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CREBZF, a multifunction transcriptional regulator, participates in the regulation of numerous cellular functions. The aims of the present study were to detect the localization of CREBZF expression in the ovary and explore the role of CREBZF and related mechanisms in the apoptosis of ovarian granulosa cells. We found by immunohistochemistry that CREBZF was mainly located in granulosa cells and oocytes during the estrous cycle. Western blot analysis showed that SMILE was the main isoform of CREBZF in the ovary. The relationship between apoptosis and CREBZF was assessed via CREBZF overexpression and knockdown. Flow cytometry analysis showed that CREBZF induced cell apoptosis in granulosa cells. Western bolt analysis showed that overexpression of CREBZF upregulated BAX and cleaved Caspase-3, while it downregulated BCL-2. Furthermore, overexpression of CREBZF inhibited the ERK1/2 and mTOR signaling pathways through the phosphorylation of intracellular-regulated kinases 1/2 (ERK1/2) and p70 S6 kinase (S6K1). Moreover, we found that CREBZF also activated autophagy by increasing LC3-II. In summary, these results suggest that CREBZF might play a proapoptotic role in cell apoptosis in granulosa cells, possibly by regulating the ERK1/2 and mTOR signaling pathways.

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“…Furthermore, it also has a certain regulatory effect on androgen secretion. Previous studies have shown that Tanshinone can not only regulate the expression of key enzymes related to androgen biosynthesis but also regulate extracellular signal-regulated kinase (ERK)/C-FOS/17, 20-lyase (CYP17), leading to androgen biosynthesis levels being down [ 118 , 119 ]. However, it is worth noting that, in addition to having similar pharmacological effects, Tanshinone has other advantages over existing anti-male drugs.…”

Section: Molecular Targets Of Tanshinone Actionmentioning

confidence: 99%

Molecular Mechanism of Tanshinone against Prostate Cancer

Li¹,

Huang²,

Xu³

et al. 2022

Molecules

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Prostate cancer (PCa) is the most common malignant tumor of the male urinary system in Europe and America. According to the data in the World Cancer Report 2020, the incidence rate of PCa ranks second in the prevalence of male malignant tumors and varies worldwide between regions and population groups. Although early PCa can achieve good therapeutic results after surgical treatment, due to advanced PCa, it can adapt and tolerate androgen castration-related drugs through a variety of mechanisms. For this reason, it is often difficult to achieve effective therapeutic results in the treatment of advanced PCa. Tanshinone is a new fat-soluble phenanthraquinone compound derived from Salvia miltiorrhiza that can play a therapeutic role in different cancers, including PCa. Several studies have shown that Tanshinone can target various molecular pathways of PCa, including the signal transducer and activator of transcription 3 (STAT3) pathway, androgen receptor (AR) pathway, phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, and mitogen-activated protein kinase (MAPK) pathway, which will affect the release of pro-inflammatory cytokines and affect cell proliferation, apoptosis, tumor metabolism, genomic stability, and tumor drug resistance. Thus, the occurrence and development of PCa cells are inhibited. In this review, we summarized the in vivo and in vitro evidence of Tanshinone against prostate cancer and discussed the effect of Tanshinone on nuclear factor kappa-B (NF-κB), AR, and mTOR. At the same time, we conducted a network pharmacology analysis on the four main components of Tanshinone to further screen the possible targets of Tanshinone against prostate cancer and provide ideas for future research.

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Cryptotanshinone Regulates Androgen Synthesis through the ERK/c‐Fos/CYP17 Pathway in Porcine Granulosa Cells

Cited by 9 publications

References 44 publications

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model

Activation of CREBZF Increases Cell Apoptosis in Mouse Ovarian Granulosa Cells by Regulating the ERK1/2 and mTOR Signaling Pathways

Molecular Mechanism of Tanshinone against Prostate Cancer

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