Abstract:
:Curcumin (diferulolylmethane), an active ingredient derived from the rhizome of the plant Curcuma longa, has anticancer activity in vitro and in vivo. Although curcumin possesses chemopreventive properties against several types of cancer, the molecular mechanisms by which it inhibits cell growth and induces apoptosis are not clearly understood. Our data revealed that curcumin inhibited growth and induced apoptosis in androgen-dependent and -independent prostate cancer cells, but had no effect on normal human prostate epithelial cells. Curcumin downregulated the expression of Bcl-2, and Bcl-XL and upregulated the expression of p53, Bax, Bak, PUMA, Noxa, and Bim. Curcumin upregulated the expression of p53 as well as its phosphorylation at serine 15, and acetylation in a concentration-dependent manner. Acetylation of histone H3 and H4 was increased in cells treated with curcumin, suggesting histone modification may regulate gene expression. Treatment of LNCaP cells with curcumin resulted in translocation of Bax and p53 to mitochondria, production of reactive oxygen species, drop in mitochondrial membrane potential, release of mitochondrial proteins (cytochrome c, Smac/DIABLO and Omi/HtrA2), activation of caspase-3 and induction of apoptosis. Furthermore, curcumin inhibited expression of phosphatidyl-inositol-3 kinase (PI3K) p110 and p85 subunits, and phosphorylation of Ser 473 AKT/PKB. Downregulation of AKT by inhibitors of PI3K (Wortmannin and LY294002) and AKT, or by dominant negative AKT increased curcumin-induced apoptosis, whereas transfection of constitutively active AKT attenuated this effect. Similarly, wild-type phosphatase and tensin homolog deleted from chromosome 10 (PTEN) enhanced curcumin-induced apoptosis and, in contrast, inactive PTEN (G129E and G129R) inhibited curcumin-induced apoptosis. Overexpression of constitutively active AKT inhibited curcumin-induced p53 translocation to mitochondria, and Smac release to cytoplasm, whereas inhibition of AKT by dominant negative AKT enhanced curcumin-induced p53 translocation to mitochondria and Smac release. Our study establishes a role for AKT in modulating the direct action of p53 on the caspase-dependent mitochondrial death pathway and suggests that these important biological molecules interact at the level of the mitochondria to influence curcumin sensitivity. These properties of curcumin strongly suggest that it could be used as a cancer chemopreventive agent.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Shankar S,Srivastava RKsubject
Has Abstractpub_date
2007-04-01 00:00:00pages
905-18issue
4eissn
1019-6439issn
1791-2423journal_volume
30pub_type
杂志文章abstract::Our study reviews the central role of androgens for the development of androgen-insensitive growth in prostatic carcinoma using an individual dynamic model which emulates aspects of proliferation control. Our aim is the identification of individually proliferating cells from prostate carcinoma. Short-term cultured cel...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.7.6.1339
更新日期:1995-12-01 00:00:00
abstract::SAC3 domain containing 1 (SAC3D1) has been reported to be involved in numerous types of cancer. However, the role of SAC3D1 in GC has not yet been elucidated. In the present study, the mRNA expression level of SAC3D1 between GC and normal tissues were assessed with a continuous variable meta‑analysis based on multiple...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5048
更新日期:2020-07-01 00:00:00
abstract::The p16INK4A tumor suppressor gene is frequently inactivated in non-small cell lung carcinoma (NSCLC) and is less frequently inactivated in small cell lung carcinoma (SCLC) by mutation, deletion or DNA methylation. There are several reports that the reintroduction of the p16INK4A gene into p16(-) NSCLC cells results i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.6.1075
更新日期:1999-06-01 00:00:00
abstract::Idarubicin (IDA) is a 4-demethoxy-anthracycline analogue of daunorubicin (DNR). IDA has been recognized as a potent anti-leukemic agent. However, the molecular mechanism of IDA-induced cell death remains unclear. In the present study, we investigated the activity of IDA to induce apoptosis in human leukemia HL-60 and ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.6.1127
更新日期:2001-12-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is thought to be a key step for cancer metastasis. Using an immunohistochemical approach with gastric carcinoma tissue, we found the expression of protease-activated receptor-1 (PAR1), along with a metalloproteinase known to activate PAR1, were associated with poorer prognosis, ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2651
更新日期:2014-12-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is typified by translocation t(11;14)(q13;q32) causing upregulation of cyclin D1 and deregulation of cell cycle. The cyclin D1 activation plays a critical role in MCL pathogenesis but additional oncogenic events, such as aberrations of the ARF/MDM2/p53 pathway are also necessary for progress...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000545
更新日期:2010-03-01 00:00:00
abstract::This study defines the role of WWOX in the regulation of epithelial to mesenchymal transition. A group of 164 endometrial adenocarcinoma patients was studied as well as an ECC1 well-differentiated steroid-responsive endometrial cell line, which was transducted with WWOX cDNA by a retroviral system. The relationship be...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2964
更新日期:2015-01-01 00:00:00
abstract::Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellul...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract::A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3536
更新日期:2016-08-01 00:00:00
abstract::We found that a mouse p53 cDNA clone (pP53-5; Jenkins et al, Nature 312: 651-654, 1984), which previously was characterized as encoding mutant p53 protein, in fact represents wild-type mouse p53 cDNA, as we were able to demonstrate that the mutations described represented sequencing artefacts (compressions). Such sequ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.1.23
更新日期:1993-07-01 00:00:00
abstract::Cytokine production in squamous cell carcinoma (SCC) of the head and neck may directly influence the clinical behavior of this aggressive neoplasm since cytokines act as autocrine/paracrine growth factors, as well as immunomodulators. In the present study, the cytokine profiles of 16 SCCs of the head and neck and matc...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Paclitaxel (taxol) has been used for the treatment of various human tumors and is an exceedingly efficient chemotherapy agent against esophageal cancer. However, the precise molecular mechanisms of paclitaxel effects on human esophageal adenocarcinoma cells are not well understood. MTT assay and cell cycle analysis we...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1135
更新日期:2011-12-01 00:00:00
abstract::p57KIP2, the second class of KIP family protein, is one of the negative regulators of the cell cycle. To elucidate the role of p57KIP2 in colorectal normal mucosa and cancer, we examined the expression of p57KIP2 protein in 110 pairs of colorectal non-tumor and cancer tissues. Immunohistochemical analysis showed that ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.1.39
更新日期:2001-07-01 00:00:00
abstract::Singlet oxygen (1O2) generated by ultraviolet A irradiation has been reported to induce cytokine-dependent Matrix metalloproteinase-1 (MMP-1) expression in dermal fibroblasts. In the present study, we analyzed the effect of hypericin-based photodynamic therapy (PDT) on MMP-1 expression in two nasopharyngeal cancer (NP...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::As epidemiological data suggest ultraviolet (UV) radiation to be the major environmental factor for the development of melanoma, we screened this malignancy for UV-specific C right curved arrow T and CC right curved arrow TT DNA mutations as described in squamous and basal cell carcinomas of the skin. Mitochondrial (m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::Seaweeds are commonly used as functional foods and drugs. A glycoprotein (GP) from the green alga Capsosiphon fulvescens (Cf) has been reported to have antitumor activity toward various cancer cells. We previously observed that Cf-GP induced different pathways of apoptosis in AGS human gastric cancer cells. Transformi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2055
更新日期:2013-10-01 00:00:00
abstract::We previously discovered the coexistence of dormant and proliferating cancer stem cells (CSCs) in gastrointestinal cancer, which leads to chemoradiation resistance. CD13-/CD90+ proliferating liver CSCs are sensitive to chemotherapy, and CD13+/CD90- dormant CSCs have a limited prolif...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1531
更新日期:2012-09-01 00:00:00
abstract::Human breast cancer is a major cause of global morbidity and mortality in women and it is a process that involves numerous molecular and cellular alterations attributed to environmental substances and agents such as hormones. Bisphosphonates, such as pamidronate, are potent antiresorptive drugs used to the treatment o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2955
更新日期:2015-01-01 00:00:00
abstract::Subsequent to the publication of the above article, the authors have realized that there were errors associated with Figs. 1c and 2b. In Fig. 1c, the authors noted that the same data were incorrectly presented for the 'Untreated cells" and 'DMSO' dot‑blot experiments. After having re‑examined their source data, the au...
journal_title:International journal of oncology
pub_type: 杂志文章,已发布勘误
doi:10.3892/ijo.2019.4874
更新日期:2019-12-01 00:00:00
abstract::Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms ar...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2885
更新日期:2015-04-01 00:00:00
abstract::In the study of 69 matched pairs of lung tumors and normal lung parenchyma, the median activities of cathepsin B (CB) and cystein proteinase inhibitors (CPI's) in tumors were found to be increased 4.4-fold and twofold, respectively. The levels of CB and CPI activities did not correlate with TNM stages nor with cell di...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.1.77
更新日期:1994-07-01 00:00:00
abstract::We have assessed the prognostic significance of mutations in the p53 tumor suppressor gene in patients with small non-cleaved cell lymphomas. In this retrospective pilot study we have, been able to evaluate the response to therapy of 21 previously untreated patients. Seven of these patients (33%) had tumors which cont...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.3.567
更新日期:1994-03-01 00:00:00
abstract::Although several therapeutic options are available for hepatocellular carcinoma (HCC), the outcome is still very poor. One reason is the complexity of signal transduction in the pathogenesis of HCC. The aim of this study was to identify new HCC-related genes and to investigate the functions of these genes in the patho...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2445
更新日期:2014-08-01 00:00:00
abstract::Established human breast cancer cell lines are widely used as experimental models in breast cancer research. While these cell lines and their variants share many phenotypic characteristics with human breast tumors, the extent to which they reflect the underlying molecular biology of breast cancer remains controversial...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract::MicroRNAs can govern up to hundred different mRNAs and are important regulators of gene expression programs in development and disease. We analyzed the expression of microRNA-21, one of the most common oncomirs, in non-small cell lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of NSCLC-deri...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2272
更新日期:2014-04-01 00:00:00
abstract::Bone is a common site of osteolytic and richly vascularized metastases of renal cell carcinoma (RCC) and Interferon (IFN)-alpha based therapies have been considered for the treatment of patients affected by this disease. The effects of IFN-alpha on metastatic RCC patients have been related to its immunomodulatory, and...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-02-01 00:00:00
abstract::EMMPRIN (extracellular matrix metalloproteinase inducer)/CD147, a membrane-bound glycoprotein with two extracellular loop domains (termed loops I and II), progresses tumor invasion and metastasis by increasing the production of matrix metalloproteinase (MMP) in peritumoral stoma cel...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1224
更新日期:2012-01-01 00:00:00
abstract::The presence of tumor cells in the bone marrow (BM) could be relevant to identifying high risk of disease progression and death in gastrointestinal cancer. However, the molecular profile associated with disseminated tumor cells (DTCs) homing to the BM has yet to be defined. MicroRNAs (miRNA) play key roles in cellular...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1112
更新日期:2011-11-01 00:00:00
abstract::Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in Martinique and Guadeloupe in order to elucidate the aetiology of prostate cancer. In 2002, world age standardized rates of prostate cancer were 152 new cases per 100,000 person-years in the two islands; one of the highest ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000229
更新日期:2009-04-01 00:00:00