Ghrelin inhibits proliferation and increases T-type Ca2+ channel expression in PC-3 human prostate carcinoma cells

Díaz‐Lezama, Nundehui; Hernández-Elvira, Mariana; Sandoval, Alejandro; Monroy, Alma O; Felix, Ricardo; Monjaraz, Eduardo

doi:10.1016/j.bbrc.2010.10.100

Cited by 44 publications

(38 citation statements)

References 20 publications

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“…Although the mechanism responsible for the link between the CPA-induced apoptosis and Ca v 3.1 expression is unknown, CPA elicited the increase in Ca v 3.1-positive cells, suggesting a pathway mediated via Ca v 3.1 channels from the activity of the genotoxic drug to apoptosis. A recent study consistent with our results indicated that Ca v 3.1 channels are involved in apoptosis in tumor cells (12). They showed that ghrelin, a multifunctional peptide hormone, significantly decreased proliferation and induced apoptosis in PC-3 human prostate carcinoma cells; these processes were prevented by T-type channel antagonists.…”

Section: Discussionsupporting

confidence: 92%

“…Ca v 3.1 may act as a growth regulator and may be a useful target for controlling cancer, if, for example, the expression of Ca v 3.1 channels could be induced. Anti-cancer agents or drugs/substances with the ability to activate the expression of Ca v 3.1 channels, such as ghrelin (12), may already exist, and a pharmacological search for such reagents may be a useful future direction for anticancer strategies.…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, the CACNA1G gene is regarded as a marker of the CpG island methylation phenotype (CIMP) for identifying specific clinicopathological features and determining the prognosis of patients with cancer. Furthermore, in prostate carcinoma cells, an increase in T-type Ca v 3.1 channel expression has been found to correlate with the inhibition of proliferation and the promotion of apoptosis (12). Alternatively, a number of reports have speculated on the progressive roles of T-type channels in tumor growth (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells

Ohkubo

2012

Int J Oncol

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells

Ohkubo

2012

Int J Oncol

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“…A similar increase in cell proliferation in response to ghrelin treatment was seen in the PC3 cell line in another study using lower concentrations of ghrelin, while supraphysiological levels (1000 nM) inhibited proliferation in this study (Cassoni et al 2004). Recently, a third laboratory demonstrated that ghrelin decreases proliferation and promotes apoptosis of PC3 cells (Diaz-Lezama et al 2010). In this study, however, the investigators measured tritiated thymidine incorporation (DNA synthesis) in the last 6 h of a 72-h ghrelin treatment, and it is unlikely that ghrelin would have been intact at this point of the experiment.…”

Section: Discussionsupporting

confidence: 85%

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Seim¹,

Lubik²,

Lehman³

et al. 2012

Journal of Molecular Endocrinology

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Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homoeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 amino acid preproghrelin isoform that codes for ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia have been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate-resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.

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“…In particular, some studies support the idea that AG increases prostate cell line proliferation (Jeffery et al 2005), which could be mediated through the activation of key signaling pathways such as MAPK/ERK and/or PI3K/AKT/mTOR (Yeh et al 2005), and protects against actinomycin D-induced apoptosis (Yeh et al 2005). Conversely, other studies have reported an antiproliferative and proapoptotic effect of AG in prostatic cancer cells (Diaz-Lezama et al 2010, Lawnicka et al 2012. As these studies employed different concentrations of AG, it has been postulated that the physiological levels of AG could act as a positive factor for prostate cells growth, while supra-physiological levels could exert an inhibitory effect.…”

Section: Adrenal Tumorsmentioning

confidence: 89%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

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Ghrelin inhibits proliferation and increases T-type Ca2+ channel expression in PC-3 human prostate carcinoma cells

Cited by 44 publications

References 20 publications

T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells

T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

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