The Role of Curcumin in Cancer Treatment.
Ontology highlight
ABSTRACT:
SUBMITTER: Zoi V
PROVIDER: S-EPMC8464730 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer.
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Project description:The incidence of bladder cancer (BC) is increasing, and although current therapeutic approaches are effective in many cases, recurrence of BC is common. Therefore, it seems necessary to search not only for novel therapeutic approaches, but also for new therapeutic agents. Natural polyphenols, such as curcumin (CUR) and epigallocatechin gallate (EGCG), possess remarkable antitumor activity. Their biochemical mechanisms of action include regulation of signaling pathways, modeling of proteins involved in apoptosis and cell cycle inhibition, angiogenesis, and the proliferation, migration and adhesion of tumor cells. Both compounds also present antioxidant, anti-inflammatory, antibacterial and antiviral properties. CUR has been considered a promising candidate for the treatment of cystic fibrosis, Alzheimer's disease or malaria, whereas EGCG can play a supportive role in the treatment of obesity, metabolic and neurodegenerative diseases. The review summarizes the latest research on the role of CUR and EGCG in the treatment of BC. In particular, the effects of CUR and EGCG, and their prospects for use in BC therapy, their inhibition of cancer development and their prevention of multidrug resistance, are described. The literature's data indicate the possibility of achieving the effect of synergism of both polyphenols in BC therapy, which has been observed so far in the treatment of ovarian, breast and prostate cancer.
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Project description:Cancer development is associated with the deregulation of various cell signaling pathways brought on by certain genetic and epigenetic alterations. Therefore, novel therapeutic strategies have been developed to target those pathways. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) pathway is one major deregulated pathway in various types of cancer. Several anticancer drug candidates are currently being investigated in preclinical and/or clinical studies to target this pathway. Natural bioactive compounds provide an excellent source for anticancer drug development. Curcumin and plumbagin are two potential anticancer compounds that have been shown to target the PI3K/Akt/mTOR pathway individually. However, their combinatorial effect on cancer cells is still unknown. This study aims to investigate the synergistic effect of these two compounds on the PI3K/Akt/mTOR pathway by employing a sequential molecular docking and molecular dynamics (MD) analysis. An increase in binding affinity and a decrease in inhibition constant have been observed when curcumin and plumbagin were subjected to sequential docking against the key proteins PI3K, Akt, and mTOR. The MD simulations and molecular mechanics combined with generalized Born surface area (MM-GBSA) analyses validated the target proteins' more stable conformation when interacting with the curcumin and plumbagin combination. This indicates the synergistic role of curcumin and plumbagin against cancer cells and the possible dose advantage when used in combination. The findings of this study pave the way for further investigation of their combinatorial effect on cancer cells in vitro and in vivo models.
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Project description:Colorectal cancer (CRC) is a second leading cause of cancer deaths in the Western world. Currently there is no effective treatment except resection at a very early stage with or without chemotherapy. Of various epithelial cancers, CRC in particular has a potential for prevention, since most cancers follow the adenoma-carcinoma sequence, and the interval between detection of an adenoma and its progression to carcinoma is usually about a decade. However no effective chemopreventive agent except COX-2 inhibitors, limited in their scope due to cardiovascular side effects, have shown promise in reducing adenoma recurrence. To this end, natural agents that can target important carcinogenic pathways without demonstrating discernible adverse effects would serve as ideal chemoprevention agents. In this review, we discuss merits of two such naturally occurring dietary agents-curcumin and resveratrol-for chemoprevention of CRC.
| S-EPMC3837545 | biostudies-literature
Project description:Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has showed potent anticancer and cancer prevention activity in a variety of cancers. However, the clinical translation of CUR has been significantly hampered due to its extensive degradation, suboptimal pharmacokinetics, and poor bioavailability. To address these clinically relevant issues, we have developed a novel CUR-loaded magnetic nanoparticle (MNP-CUR) formulation. Herein, we have evaluated the in vitro and in vivo therapeutic efficacy of this novel MNP-CUR formulation in pancreatic cancer. Human pancreatic cancer cells (HPAF-II and Panc-1) exhibited efficient internalization of the MNP-CUR formulation in a dose-dependent manner. As a result, the MNP-CUR formulation effectively inhibited growth of HPAF-II and Panc-1 cells in cell proliferation and colony formation assays. The MNP-CUR formulation suppressed pancreatic tumor growth in an HPAF-II xenograft mouse model and improved the survival of mice by delaying tumor growth. The growth-inhibitory effect of MNP-CUR formulation correlated with the suppression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-extra large (Bcl-xL), induced myeloid leukemia cell differentiation protein (Mcl-1), cell surface-associated Mucin 1 (MUC1), collagen I, and enhanced membrane ?-catenin expression. MNP-CUR formulation did not show any sign of hemotoxicity and was stable after incubation with human serum proteins. In addition, the MNP-CUR formulation improved serum bioavailability of CUR in mice up to 2.5-fold as compared with free CUR. Biodistribution studies show that a significant amount of MNP-CUR formulation was able to reach the pancreatic xenograft tumor(s), which suggests its clinical translational potential. In conclusion, this study suggests that our novel MNP-CUR formulation can be valuable for the treatment of pancreatic cancer.
| S-EPMC3965353 | biostudies-literature
Project description:The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 μM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 μM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.
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Project description:Cervical cancer is the second most common cancer in women worldwide. In addition to the important role played by HPV, the underlying mechanism promoting cervical tumorigenesis is complex and involves deregulation of key signaling pathways. Recently, role of miRNA mediated abnormal regulatory mechanisms is implicated in the pathogenesis of cervical cancer. Micro RNAs are regulatory, non‐coding RNAs about 21–23 nucleotides in length and effects the expression of a number of genes at the post‐transcriptional level. For the past few decades, role of curcumin in inhibiting the growth of cervical cancer and increasing the chemo and radio- sensistivity has been studied extensively. Interestingly, curcumin was shown to downregulate NF-κB, Wnt/β-catenin, TGF‐β and various other signaling pathways in cervical cancer cells. Although, a number of microarray studies have examined the use of miRNAs as cancer diagnostic markers, the regulation of miRNAs upon treatment with curcumin in cervical cancer cells has not been studied. The current study is aimed to perform miRNA profiling in cervical cancer cells following curcumin treatment and to study the role of miRNAs in regulating the different signaling pathways.
2022-06-30 | GSE134723 | GEO
Project description:HER2+ breast cancer cells were treated with curcumin analog PGB-0-ol and analyzed mRNA expression through mRNA sequencing
2022-11-26 | GSE218021 | GEO
Project description:A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids.
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Project description:The diarylheptanoid curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] is one of the phenolic pigments responsible for the yellow colour of turmeric (Curcuma longa L.). This phytochemical has gained much attention in recent years due to its therapeutic potential in cancer. A range of drug delivery approaches have been developed to optimise the pharmacokinetic profile of curcumin and ensure that it reaches its target sites. Curcumin exhibits numerous biological effects, including anti-inflammatory, cardioprotective, antidiabetic, and anti-aging activities. It has also been extensively studied for its role as a cancer chemopreventive and anticancer agent. This review focusses on the role of curcumin in targeting the cell signalling pathways involved in cancer, particularly via modulation of growth factors, transcription factors, kinases and other enzymes, pro-inflammatory cytokines, and pro-apoptotic and anti-apoptotic proteins. It is hoped that this study will help future work on the potential of curcumin to fight cancer.
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