The inhibitory effect of Curcuma longa extract on telomerase activity in A549 lung cancer cell line (original) (raw)

Curcumin induced cell death and inhibition of telomerase activity in mouse lymphoma P388D1 cells

2009

Telomerase, a potential marker for tumorigenesis, has been found to be activated in more than 85-90% of human cancer. Curcumin is the major biologically active, yellow phytochemical compound of Curcuma longa (Zingiberaceae). The present study is aimed to investigate the capacity of curcumin on the regulation of telomerase activity and induction of apoptosis in P388D1 mouse lymphoma cells. Here, we demonstrate that curcumin at a concentration of 3.5 µM and an incubation period of 48h induces apoptosis and inhibits telomerase activity in the P388D1 cells. Curcumin induced apoptosis and telomerase activity in P388D1 lymphoma cells was confirmed by enumeration of apoptotic cells, % DNA fragmentation and RT-PCR. The culture supernatant of lymphoma cells treated with curcumin showed a higher level of nitric oxide content. RT-PCR analysis revealed over expression of TNF-α and IL-1β and inhibition of the antiapoptotic Bcl-2 and human catalytic subunit hTERT in the curcumin treated lymphoma cells as compared to untreated cells. Taken together the result shows that curcumin could significantly inhibit tumor proliferation and induce apoptosis in lymphoma cells. Thus, curcumin should be further tested as a possible antineoplastic agent.

Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line

Cancer Letters, 2002

The inhibitory effect of curcumin, the yellow-colored pigment from turmeric, on telomerase activity was analyzed in human mammary epithelial (MCF-10A) and breast cancer (MCF-7) cells. Telomerase activity in MCF-7 cells is 6.9-fold higher than that of human mammary epithelial cells. In MCF-7 cells, telomerase activity decreased with increasing concentrations of curcumin, inhibiting about 93.4% activity at 100 mM concentration. The inhibition of telomerase activity in MCF-7 cells may be due to down-regulation of hTERT expression. Increasing concentrations of curcumin caused a steady decrease in the level of hTERT mRNA in MCF-7 cells whereas the level of hTER and c-myc mRNAs remained the same. Our results suggest that curcumin inhibits telomerase activity by down-regulating hTERT expression in breast cancer cells and this down-regulation is not through the c-myc pathway.

Curcumin and silibinin inhibit telomerase expression in T47D human breast cancer cells

Asian Pacific journal of cancer prevention : APJCP, 2013

Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.

Evaluation of Anti-oxidant and Anti-cancer Activity of Cultivated Yemeni Curcuma Longa L. Extracts on Skin (A431) and Lung (A549) Cancer Cell Lines

International Journal of Research and Development in Pharmacy & Life Sciences, 2022

Abstract Background: Turmeric (Hurud) is one of the cultivated medical plants in Yemen in various geographical areas mountainous highlands such as Mohaweet, where the plant of this study was collected. This plant is used in alternative medicine in Yemen as preparation for skin cosmetics. This study was designed to evaluate the chemical composition, antioxidant and anticancer activities of Yemeni Curcuma fractions against two human cancer cell lines were used (A431 skin cancer and A549 lung cancer cell line). Methods: Tumeric fractions were tested for their chemical analysis using Fourier Transform Infrared (FTIR) and Spectral analysis (Ultra violate analysis). The antioxidant activity of all selected extracts was evaluated by DPPH and FBAAC methods. The cytotoxicity of the fractions was determined on two human cancer cell lines were used (A431 skin cancer and A549 lung cancer cell line). and noncancerous using the tetrazolium-based colorimetric (MTT) assay. Vinblastine, a broad-spectrum anticancer drug was used as a positive control to assess the cytotoxic activity of extract and oils. The potential mechanism of action of the active fractions was apoptosis. Results: The cells viability results of this study showed that the use of ethyl acetate fraction of local cultivated Yemeni Curcuma longa extract has high activity on the viability of A431skin cancer and A 549 lung cancer cell line compared with untreated cells and the activity was high whenever the concentration is high, followed by acetone extract, whereas crude turmeric had the lowest activity. The morphological examination using crystal violates stain results in an adverse relationship between the extract concentration and the number of cancer cells compared with control.

Curcuminoid derivatives enhance telomerase activity in an in vitro TRAP assay

Bioorganic & Medicinal Chemistry Letters, 2014

The length of telomeres controls the life span of eukaryotic cells. Telomerase maintains the length of telomeres in certain eukaryotic cells, such as germline cells and stem cells, and allows these cells to evade replicative senescence. Here, we report for the first time a number of curcuminoid derivatives that enhance telomerase activity in an in vitro TRAP assay. A preliminary analysis of structure-activity relationships found that the minimal requirement for this enhanced telomerase activity is a curcuminoid core with at least one n-pentylpyridine side chain, while curcuminoids with two such side chains exhibit even greater activity. The finding here might lead to a new class of telomerase activators that act directly or indirectly on telomerase, rather than through the reactivation of the telomerase reverse transcriptase (TERT) gene associated with other telomerase activators found in the literature.

N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells

Curcumin is a natural compound that has been extensively observed due to its potential as an anticancer drug. Curcumin restrains cancer cell progression via telomerase activity suppression. However, the exact mechanism is still unknown. In this study, we demonstrate that the effects of curcumin on cell viability and telomerase activity can be blunted by reactive oxygen species (ROS) inhibitor N-acetyl cysteine (NAC). The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RT-PCR, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin. Sp1 is one of the important transcription factors in hTERT expression. Our data showed that curcumin decreases the expression of Sp1 through proteasome pathway. In addition, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin. Further, reporter assay and DNA affinity precipitation assay confirmed the influence of curcumin on Sp1 in hTERT regulation. This is the first study to demonstrate that curcumin induces ROS production resulting in Sp1 binding activity inhibition and hTERT downregulation.

Antiproliferative Effects of Cucurbitacin B in Breast Cancer Cells: Down-Regulation of the c-Myc/hTERT/Telomerase Pathway and Obstruction of the Cell Cycle

International Journal of …, 2010

Naturally occurring cucurbitacins have been shown to have anticancer, antimicrobial and anti-inflammatory activities. In this study, we determined the effects of cucurbitacin B extracted from the Thai herb Trichosanthes cucumerina L. on telomerase regulation in three human breast cancer cell lines (T47D, SKBR-3, and MCF-7) and a mammary epithelium cell line (HBL-100). Cell viability after treatment with cucurbitacin B, which is an active ingredient of this herb, was assessed. Telomeric Repeat Amplification Protocol (TRAP) assays and RT-PCR (qualitative and realtime) were performed to investigate activity of telomerase as well as expression of human telomerase reverse transcriptase (hTERT) and c-Myc. The c-Myc protein level was also determined in SKBR-3 and HBL-100 cells. Our results show that the cucurbitacin B inhibits growth and telomerase activity in the three breast cancer cell lines and exerts an obvious inhibitory effect in the estrogen receptor (ER)-negative breast cancer SKBR-3 cells. The expression of hTERT and c-Myc were also inhibited by cucurbitacin B, In addition, a clear reduction of c-Myc protein was observed after treatment in SKBR-3 cells even with a concentration of

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

Food and Chemical Toxicology, 2010

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0-41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of arturmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent.