gingerol and Breast-Neoplasms

Ginger, the rhizome of Zingiber officinalis, one of the most widely used species of the ginger family, is a common condiment for various foods and beverages. Ginger has a long history of medicinal use dating back 2500 years. Ginger has been traditionally used from time immemorial for varied human ailments in different parts of the globe, to aid digestion and treat stomach upset, diarrhoea, and nausea. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory activities, and some of them exhibit cancer preventive activity in experimental carcinogenesis. The anticancer properties of ginger are attributed to the presence of certain pungent vallinoids, viz. [6]-gingerol and [6]-paradol, as well as some other constituents like shogaols, zingerone etc. A number of mechanisms that may be involved in the chemopreventive effects of ginger and its components have been reported from the laboratory studies in a wide range of experimental models.

Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Catechols; Colonic Neoplasms; Fatty Alcohols; Gastrointestinal Neoplasms; Guaiacol; Humans; Ketones; Oils, Volatile; Skin Neoplasms; Tumor Cells, Cultured; Zingiber officinale

Multiple potential drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated gingerol-loaded niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human breast cancer cells. The preparation procedure was modified by adjusting the drug concentration, lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the gingerol-loaded niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed drug diffusion at physiological pH and significant drug diffusion under acidic conditions (pH = 5.4), making it a promising option for cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3 breast cancer cells, attributed to the presence of gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and VEGF genes, along with up-regulation of the expression of BAX, CASP9, CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible niosomes in the future of nanomedicine, enabling more precise and effective treatment of cancers.

Topics: Breast Neoplasms; Female; Humans; Hydrogen-Ion Concentration; Liposomes; Polyethylene Glycols; Proto-Oncogene Proteins c-bcl-2

Breast cancer is one of the most common malignant neoplasms, and despite the dynamic development of anticancer therapies, 5-year survival in the metastatic stage is still less than 30%. 6-Gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) is a substance contained in ginger, which exhibits anti-cancer properties. Paclitaxel is a cytostatic substance used to treat breast cancer, but its therapeutically effective dose has many adverse effects. The aim of the presented study was to assess the anticancer effect of 6-gingerol and the possibility of increasing the effectiveness of Paclitaxel in the death induction of wild type human breast cancer cells. MCF-7/WT cells were treated with drugs-6-gingerol and paclitaxel at selected concentrations. The mitochondrial activity assay, caspase 7 activity assay, ATP assay, microscopy studies, and RT-PCR assays were performed to evaluate the antitumor activity and mechanism of action of both compounds, alone and in combination. After 72 h of incubation, the mitochondrial activity showed that the combination of 5 nM Paclitaxel with 10 µM 6-Gingerol led to the same decrease in viability as the use of 20 nM Paclitaxel alone; 10 µM 6-Gingerol led to an enhancement of caspase 7 activity, with the highest activity observed after 24 h of incubation. A real-time PCR study showed that 6-Gingerol induces the simultaneous transcription of Bax with TP53 genes in large excess to BCL-2. In contrast, 5 nM Paclitaxel induces TP53 transcription in excess of BCL-2 and Bax. Our results suggest that 6-Gingerol may act as a cell death-inducing agent in cancer cells and, in combination with paclitaxel, and increase the effectiveness of conventional chemotherapy.

Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Caspase 7; Catechols; Cell Line, Tumor; Fatty Alcohols; Female; Humans; Paclitaxel

Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Catechols; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; DNA Damage; ErbB Receptors; Fatty Alcohols; Female; Humans; MCF-7 Cells; Mitochondria; Models, Biological; Reactive Oxygen Species; Signal Transduction; Spheroids, Cellular; src-Family Kinases; STAT3 Transcription Factor; Tumor Suppressor Protein p53; Zingiber officinale

6-Gingerol (6G) and 6-Shogaol (6S) are the main active components of ginger. 6-Gingerol is known for its anti-metastatic and anti-invasive pharmacological activities on cancer cells, besides, 6-Shogaol also inhibits breast cancer cell invasion.. In this study, radioiodination (131I) of 6G and 6S was aimed. Additionally, it is aimed to monitor their incorporation behavior on breast cancer cell lines.. 6-Gingerol was isolated from the fresh ginger-roots extract, additionally, dehydrated to obtain 6-Shogaol. 6G and 6S were radioiodinated using iodogen method. Quality control studies of radioiodinated ginger compounds (6G and 6S) were performed by thin layer radio-chromatography. In vitro studies of radioiodinated ginger compounds on MCF-7 and MDA-MB-231 cells were performed with incorporation assays.. 6-Gingerol and 6-Shogaol were radioiodinated (131I-6G and 131I-6S) in high yields over 95%. 131I-6S demonstrated higher incorporation values than 131I-6G on MDA-MB-231 cells. Incorporation behavior of 131I-6G and 131I-6S was similar to MCF-7 cells.. It has been observed that ginger compounds were radioiodinated successfully and 131I-6S have a noteworthy incorporation on MDA-MB-231 cells which is a known breast carcinoma cell line with highly invasive characteristics.

Topics: Breast Neoplasms; Catechols; Chromatography, Thin Layer; Fatty Alcohols; Female; Humans; Iodine Radioisotopes; Molecular Structure; Tumor Cells, Cultured; Zingiber officinale

Background: Cancer is a significant problem in modern medicine, also is the most common cause of death after\ cardiovascular diseases, and in need of targeted drug release. Although, chemotherapy is an important candidate in\ cancer treatment, but it has many side effects on healthy tissues of the body. Therefore, Nano technology is used\ for specific function, by the least side effects and damage to normal cells. Materials and method: In this study, the\ pharmacological properties of PEGylated Nano-niosomal Gingerol was examined. Noisome were prepared using reverse\ phase evaporation method, which contains specific proportion of cholesterol, span60 and polyethylene glycol. Then,\ PEGylated the prepared formulation by PEG6600. The amount of release and encapsulation of the drug was investigated.\ The percentage of remains of cancer cell line T47D treated with PEGylated niosomal Gingerol. Results: The average\ diameter of the nanoparticles, size distribution and zeta potential were reported for PEGylated niosomal sample 35.65\ nm, 0.17 and 21 mv, and for PEGylated niosomal drug sample 256.9 nm, 0.23 and 28 mv, respectively. The amount\ of OD for encapsulated drug was 0.198, also the amount of concentration of the drug which is not encapsulated, was\ 0.77947 μl of the drug per ml. This value of encapsulated drug was 76.38 percent. Conclusion: The results showed that\ IC50 of the formulation of PEGylated nanoniosomal Gingerol is less than the standard drug. It seems, the cause of this\ phenomenon is due to the effect of Polyethylene glycol, in more stability and slower drug release, in the formulation\ of PEGylated niosome. Also, Polyethylene glycol makes increase in the drug dealing and its greater influence with the\ target cell. In this study, more than 76% of the Gingerol drug in PEGylated nanoniosomal formulation were enclose.\ Also, we could reduce the amount of drug release, as much as possible.

Topics: Antineoplastic Agents; Breast Neoplasms; Catechols; Cell Proliferation; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Fatty Alcohols; Female; Humans; In Vitro Techniques; Liposomes; Nanoparticles; Polyethylene Glycols; Tumor Cells, Cultured

In the present study, we investigated the roles and molecular mechanism of 10-gingerol, a phenolic compound isolated from Zingiber officinale, in regulating cell proliferation and invasion of MDA‑MB‑231 breast cancer cells. 10-gingerol treatment inhibited cell proliferation through downregulation of cell cycle regulatory proteins such as cyclin-dependent kinases and cyclins, and subsequent induction of G1 phase arrest. In addition, 10‑gingerol treatment blocked cell invasion in response to mitogenic stimulation. These antitumor activities of 10‑gingerol were mediated through inactivation of Akt and p38MAPK activity, and suppression of epidermal growth factor receptor expression. Collectively, these findings demonstrate the pharmacological roles of 10-gingerol in regulating breast cancer cell growth and progression, and suggest further evaluation and development as a potential therapeutic agent for the prevention and treatment of breast cancer.

Topics: Antineoplastic Agents, Phytogenic; Blotting, Western; Breast Neoplasms; Catechols; Cell Line, Tumor; Cell Proliferation; Fatty Alcohols; Female; Humans; Magnetic Resonance Spectroscopy; Neoplasm Invasiveness; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols' wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC50 = 30.4 μM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol's SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol's cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.

Topics: Antineoplastic Agents; Breast Neoplasms; Catechols; Cell Survival; Fatty Alcohols; Humans; MCF-7 Cells; Structure-Activity Relationship

Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 microM). [6]-Gingerol had no effect on cell adhesion up to 5 microM, but resulted in a 16% reduction at 10 microM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment. In conclusion, we have shown that [6]-gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.

Topics: Actins; Breast Neoplasms; Catechols; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Fatty Alcohols; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Metastasis