The potential role of curcumin in prostate cancer: the importance of optimizing pharmacokinetics in clinical studies

Schmidt, Keith T.; Figg, William D.

doi:10.21037/tcr.2016.11.04

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…It has been shown that androgen signaling alone or in combination with other signaling pathways play an important role in the development of prostate cancer, hormone resistance as wells as relapse of the disease [27,28]. The antagonistic relationship at the gene expression level was observed between AR and MYC in prostate cancer context [29]. MYC overexpression was shown to deregulate the AR transcriptional program to drive prostate tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

Katta

Srivastava

Thangapazham

et al. 2019

IJMS

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The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3–24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.

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Section: Discussionmentioning

confidence: 99%

Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

Katta

Srivastava

Thangapazham

et al. 2019

IJMS

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“…Curcumin derives from the turmeric plant and has been used as an adjuvant therapy to many diseases requiring a boost of the immune system [ 71 , 72 ]. Moreover, curcumin has been suggested to entail chemopreventive and anticancer properties related to PCa [ 73 , 74 ]. Two placebo-controlled trials ( Table 3 ) have compared curcumin ONS among patients with PCa, both failing to induce any differences in circulating PSA after 3 [ 75 ] and 6 [ 76 ] months of supplementation, respectively.…”

Section: Antioxidants and Psa Kineticsmentioning

confidence: 99%

Dietary Factors and Supplements Influencing Prostate-Specific Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials

et al. 2020

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The quest for dietary patterns and supplements efficient in down-regulating prostate-specific antigen (PSA) concentrations among men with prostate cancer (PCa) or increased PCa risk has been long. Several antioxidants, including lycopene, selenium, curcumin, coenzyme Q10, phytoestrogens (including isoflavones and flavonoids), green tea catechins, cernitin, vitamins (C, E, D) and multivitamins, medicinal mushrooms (Ganoderma lucidum), fruit extracts (saw palmetto, cranberries, pomegranate), walnuts and fatty acids, as well as combined supplementations of all, have been examined in randomized controlled trials (RCTs) in humans, on the primary, secondary, and tertiary PCa prevention level. Despite the plethora of trials and the variety of examined interventions, the evidence supporting the efficacy of most dietary factors appears inadequate to recommend their use.

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“…A persistent AR activation in AIPC leads to uncontrolled cell proliferation and metastasis, and subsequently resulting death in PCa patients [24]. Curcumin as an anti-inflammatory agent, has the capability to suppress AR at the protein as well as AR gene transcription level in PCa cells [105,116]. The effects of curcumin on AR signalling are shown in Figure 4a.…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

“…Moreover, curcumin treatment against AIPC (PC-3) cells also alter the over-expressed heat shock protein (Hsp90), resulting in the reduction of AR availability [104]. Curcumin also shows positive outcomes when tested in animal models, where it delays the tumour growth and suppresses AR expression in ADPC (LNCaP) xenograft model [105]. Another study on LNCaP xenografts models showed that curcumin inhibits AR through the modulation of Wnt/ß-catenin signalling [106].…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer

et al. 2020

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Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.

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The potential role of curcumin in prostate cancer: the importance of optimizing pharmacokinetics in clinical studies

Cited by 18 publications

References 23 publications

Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

Dietary Factors and Supplements Influencing Prostate-Specific Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials

Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer

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