Curcumin In Cancer Research Articles

Exploring the therapeutic mechanism of curcumin in prostate cancer using network pharmacology and molecular docking

ObjectiveCurcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. MethodUsing tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. ResultWe identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below −1.85 kJ mol−1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. ConclusionThrough in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.

The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway.

Cancer is a life-threatening disease and one of the leading causes of death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures have been investigated for their multimodal anti-cancer properties. Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway.

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management.

This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3β, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community.

Exploring the Contribution of Curcumin to Cancer Therapy: A Systematic Review of Randomized Controlled Trials.

Although the anticancer role of curcumin has been extensively addressed in preclinical research, only a few studies were carried out in humans, with conflicting results. The aim of this systematic review is to collate together the results of the therapeutic effect of curcumin in cancer patients. A literature search was carried out in Pubmed, Scopus, and the Cochrane Central Register of Controlled Trials up to 29 January 2023. Only randomized controlled trials (RCTs) designed to evaluate the effects of curcumin on cancer progression, patient survival, or surgical/histological response were included. Seven out of 114 articles, published between 2016 and 2022, were analyzed. They evaluated patients with locally advanced and/or metastatic prostate, colorectal, and breast cancers, as well as multiple myeloma and oral leucoplakia. Curcumin was given as an add-on therapy in five studies. Cancer response was the most investigated primary endpoint and curcumin issued some positive results. On the contrary, curcumin was ineffective in improving overall or progression-free survival. The curcumin safety profile was favorable. In conclusion, available clinical evidence is not strong enough to support the therapeutic use of curcumin in cancer. New RCTs exploring the effects of different curcumin formulations in early-stage cancers would be welcome.

Modulatory properties of curcumin in cancer: A narrative review on the role of interferons.

The immune network is an effective network of cell types and chemical compounds established to maintain the body's homeostasis from foreign threats and to prevent the risk of a wide range of diseases; hence, its proper functioning and balance are essential. A dysfunctional immune system can contribute to various disorders, including cancer. Therefore, there has been considerable interest in molecules that can modulate the immune network. Curcumin, the active ingredient of turmeric, is one of these herbal remedies with many beneficial effects, including modulation of immunity. Curcumin is beneficial in managing various chronic inflammatory conditions, improving brain function, lowering cardiovascular disease risk, prevention and management of dementia, and prevention of aging. Several clinical studies have supported this evidence, suggesting curcumin to have an immunomodulatory and anti-inflammatory function; nevertheless, its mechanism of action is still not clear. In the current review, we aim to explore the modulatory function of curcumin through interferons in cancers.

The golden spice curcumin in cancer

Curcumin, the key bioactive phytochemical present in turmeric (Curcuma longa L.), is the most studied natural compound in cancer. Preclinical studies (in vitro and in vitro) and clinical trials have demonstrated curcumin's effectiveness as an anti-inflammatory agent. The existing evidence supports that curcumin inhibits the proliferation of many types of cancer cells and can play an important role in cancer therapy. This study analyses the existing evidence in the literature on finalized clinical trials (2010-2020) related to the effect of curcumin and turmeric-derived products that focused on different types of cancers, such as chronic myeloid leukemia, multiple myeloma, prostate, colorectal and pancreatic cancer as well as cancer therapy-related complications, including oral mucositis and radiation dermatitis. Original English language articles and clinical trials published between 2010 and 2020 were searched using mainstream scholarly databases, such as PubMed, ScienceDirect, Google Scholar, and ClinicalTrials.gov. The keywords, such as "curcumin," "turmeric," "cancer," "anti-inflammatory," and "clinical trials," were used in various combinations. A total of 21 clinical trials were selected, reviewed, and included in this study. Sixteen out of 21 clinical trials were associated with the effectiveness of curcumin or turmeric on various types of cancer, and the other five clinical trials were related to the evaluation of the efficacy of curcumin or turmeric in relieving the side effects of cancer chemotherapy and radiotherapy. The emerging data from the clinical trials confirm that curcumin has the potential for cancer prevention and intervention. However, it is not yet clear whether long-term curcumin supplementation has similar benefits.

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer.

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

C-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) attenuates curcumin-induced cell death differently from its family member, JNK-associated leucine zipper protein (JLP).

Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) reduces curcumin-induced cell death by modulating p38 MAPK and autophagy through the regulation of lysosome positioning. In this study, we investigated the role of JNK/stress-activated protein kinase-associated protein 1 (JSAP1), a JLP family member, in curcumin-induced stress, and found that JSAP1 also attenuates curcumin-induced cell death. However, JSAP1 knockout showed no or little effect on the activation of JNK and p38 MAPKs in response to curcumin. In addition, small molecule inhibitors of JNK and p38 MAPKs did not increase curcumin-induced cell death. Furthermore, JSAP1 depletion did not impair lysosome positioning and autophagosome-lysosome fusion. Instead, we noticed substantial autolysosome accumulation accompanied by an inefficient autophagic flux in JSAP1 knockout cells. Taken together, these results indicate that JSAP1 is involved in curcumin-induced cell death differently from JLP, and may suggest that JSAP1 plays a role in autophagosome degradation and its dysfunction results in enhanced cell death. The findings of this study may contribute to the development of novel therapeutic approaches using curcumin for cancer.

Telomerase: A Target for Therapeutic Effects of Curcumin in Cancer.

Telomerases are attractive targets for development of new anticancer agents. Most tumors express the enzyme telomerase that maintains telomere length and thus ensures indefinite cell proliferation, a hallmark of cancer. Curcumin has been shown to be effective against several types of malignancies and has also been shown to have inhibitory effects on telomerase activity. Hence, the aim of this chapter is to review the available investigations of curcumin on telomerase activity. Based on the findings obtained from the different studies here, we conclude that the telomerase inhibitory effects of curcumin are integral to its anticancer activity, and thus curcumin may be useful therapeutically in the cancer field.

Functional drug–target–disease network analysis of gene–phenotype connectivity for curcumin in cancer

Functional drug–target–disease network analysis of gene–phenotype connectivity for curcumin in cancer

Xanthan gum stabilized PEGylated gold nanoparticles for improved delivery of curcumin in cancer

In recent years, gold nanoparticles (AuNPs) have received immense interest in various biomedical applications including drug delivery, photothermal ablation of cancer and imaging agent for cancer diagnosis. However, the synthesis of AuNPs poses challenges due to the poor reproducibility and stability of the colloidal system. In the present work, we developed a one step, facile procedure for the synthesis of AuNPs from hydrogen tetrachloroaurate (III) hydrate (HAuCl4. 3H2O) by using ascorbic acid and xanthan gum (XG) as reducing agent and stabilizer, respectively. The effect of concentrations of HAuCl4, 3H2O, ascorbic acid and methoxy polyethylene glycol-thiol (mPEG800-SH) were optimized and it was observed that stable AuNPs were formed at concentrations of 0.25 mM, 50 μM and 1 mM for HAuCl4.3H2O, ascorbic acid, and mPEG800-SH, respectively. The XG stabilized, deep red wine colored AuNPs (XG-AuNPs) were obtained by drop-wise addition of aqueous solution of ascorbic acid (50 mM) and XG (1.5 mg ml−1). Synthesized XG-AuNPs showed λmax at 540 nm and a mean hydrodynamic diameter of 80 ± 3 nm. PEGylation was performed with mPEG800-SH to obtain PEGylated XG-AuNPs (PX-AuNPs) and confirmed by Ellman’s assay. No significant shift observed in λmax and hydrodynamic diameter between XG-AuNPs and PX-AuNPs. Colloidal stability of PX-AuNPs was studied in normal saline, buffers within a pH range of 1.2–7.4, DMEM complete medium and in normal storage condition at 4 ˚C. Further, water soluble curcumin was prepared using PVP-K30 as solid dispersion and loaded on to PX-AuNPs (CPX-AuNPs), and evaluated for cellular uptake and cytotoxicity in Murine melanoma (B16F10) cells. Time and concentration dependent studies using CPX-AuNPs showed efficient uptake and decreased cell viability compared to free curcumin.

Preclinical In Vitro, In Vivo, and Pharmacokinetic Evaluations of FLLL12 for the Prevention and Treatment of Head and Neck Cancers.

Despite its high promise for cancer prevention and therapy, the potential utility of curcumin in cancer is compromised by its low bioavailability and weak potency. The purpose of the current study was to assess the in vitro and in vivo efficacy and pharmacokinetic parameters of the potent curcumin analogue FLLL12 in SCCHN and identify the mechanisms of its antitumor effect. IC50 values against a panel of one premalignant and eight malignant head and neck cancer cell lines as well as apoptosis assay results suggested that FLLL12 is 10- to 24-fold more potent than natural curcumin depending on the cell line and induces mitochondria-mediated apoptosis. In vivo efficacy (xenograft) and pharmacokinetic studies also suggested that FLLL12 is significantly more potent and has more favorable pharmacokinetic properties than curcumin. FLLL12 strongly inhibited the expression of p-EGFR, EGFR, p-AKT, AKT, Bcl-2, and Bid and increased the expression of Bim. Overexpression of constitutively active AKT or Bcl-2 or ablation of Bim or Bid significantly inhibited FLLL12-induced apoptosis. Further mechanistic studies revealed that FLLL12 regulated EGFR and AKT at transcriptional levels, whereas Bcl-2 was regulated at the translational level. Finally, FLLL12 strongly inhibited the AKT downstream targets mTOR and FOXO1a and 3a. Taken together, our results strongly suggest that FLLL12 is a potent curcumin analogue with more favorable pharmacokinetic properties that induces apoptosis of head and neck cancer cell lines by inhibition of survival proteins including EGFR, AKT, and Bcl-2 and increasing of the proapoptotic protein Bim.

Biological and therapeutic activities, and anticancer properties of curcumin.

Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

FLLL12 induces apoptosis in lung cancer cells through a p53/p73-independent but death receptor 5-dependent pathway

Unlike chemotherapy drugs, the safety of natural compounds such as curcumin has been well established. However, the potential use of curcumin in cancer has been compromised by its low bioavailability, limited tissue distribution and rapid biotransformation leading to low in vivo efficacy. To circumvent these problems, more potent and bioavailable analogs have been synthesized. In the current study, we investigated the mechanism of anti-tumor effect of one such analog, FLLL12, in lung cancers. IC50 values measured by sulforhodamine B (SRB) assay at 72 h and apoptosis assays (annexin V staining, cleavage of PARP and caspase-3) suggest that FLLL12 is 5–10-fold more potent than curcumin against a panel of premalignant and malignant lung cancer cell lines, depending on the cell line. Moreover, FLLL12 induced the expression of death receptor-5 (DR5). Ablation of the expression of the components of the extrinsic apoptotic pathway (DR5, caspase-8 and Bid) by siRNA significantly protected cells from FLLL12-induced apoptosis (p < 0.05). Analysis of mRNA expression revealed that FLLL-12 had no significant effect on the expression of DR5 mRNA expression. Interestingly, inhibition of global phosphatase activity as well as protein tyrosine phosphatases (PTPs), but not of alkaline phosphatases, strongly inhibited DR5 expression and significantly inhibited apoptosis (p < 0.05), suggesting the involvement of PTPs in the regulation of DR5 expression and apoptosis. We further showed that the apoptosis is independent of p53 and p73. Taken together, our results strongly suggest that FLLL12 induces apoptosis of lung cancer cell lines by posttranscriptional regulation of DR5 through activation of protein tyrosine phosphatase(s).

The role of phytochemicals as micronutrients in health and disease.

Intake of dietary phytochemicals has frequently been associated with health benefits. Noninfectious diseases including cardiovascular disease (CVD), cancer and diabetes are major causes of death, whereas dementia cases are also increasing to 'epidemic' proportion. This review will focus on recent progress on mechanisms underlying the potential role of dietary phytochemicals in CVD, diabetes, cancer and dementia, with consideration of the latest clinical data. The association of tea (Camellia sinensis), particularly catechins, with reported mechanistic effects for CVD, diabetes, cancer and cognition contributes to our understanding of the suggested benefits of tea consumption on health from limited and inconclusive clinical trial and epidemiological data. Resveratrol, which occurs in grapes (Vitis vinifera) and wine, and curcumin, a component of turmeric (Curcuma longa), are also emerging as potentially relevant to health, particularly for CVD and dementia, with some promising data also concluded for curcumin in cancer. Other phytochemicals mechanistically relevant for health include anthocyanins, isoflavones and glucosinolates, which are also discussed. Evidence for the role of phytochemicals in health and disease is growing, but associations between phytochemicals and disease need to be more firmly understood and established from more robust clinical data using preparations that have been phytochemically characterized.