Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo

ArticleinThe Prostate 47(4):293-303 · June 2001with84 Reads
DOI: 10.1002/pros.1074 · Source: PubMed
Abstract
Earlier work from our laboratory highlighted the therapeutic potential of curcumin (turmeric), used as a dietary ingredient and as a natural anti-inflammatory agent in India and other Southeast Asian countries. This agent was shown to decrease the proliferative potential and induce the apoptosis potential of both androgen-dependent and androgen-independent prostate cancer cells in vitro, largely by modulating the apoptosis suppressor proteins and by interfering with the growth factor receptor signaling pathways as exemplified by the EGF-receptor. To extend these observations made in vitro and to study the efficacy of this potential anti-cancer agent in vivo, the growth of LNCaP cells as heterotopically implanted tumors in nude mice was followed. The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received a synthetic diet containing 2% curcumin for up to 6 weeks. At the end point, sections taken from the excised tumors were evaluated for pathology, cell proliferation, apoptosis, and vascularity. Curcumin causes a marked decrease in the extent of cell proliferation as measured by the BrdU incorporation assay and a significant increase in the extent of apoptosis as measured by an in situ cell death assay. Moreover, a significant decrease in the microvessel density as measured by the CD31 antigen staining was also seen. Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth, as exemplified by LNCaP in vivo, and has the potential to prevent the progression of this cancer to its hormone refractory state.
    • "The antitumor activity of curcumin is thought to be mediated through multiple mechanisms. At the molecular level, curcumin is known to induce apoptosis in a wide array of cancer cells including human colon, stomach, liver, breast, and prostate cancers [7][8][9][10][11] . It is known to mediate its effects by inhibition of anti-apoptotic markers such as Bcl-2, Bcl-xL, Survivin, and increased expression of pro-apoptotic factors such as Bax, Bad, Bak, PUMA, Bim, Noxa and TRAIL-R1 [12][13][14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Curcumin, derived from the rhizome Curcuma longa, is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still lacking. In this study, we carried out SILAC-based quantitative proteomic analysis of a HNSCC cell line (CAL 27) to investigate tyrosine signaling in response to curcumin. Results Using high resolution Orbitrap Fusion Tribrid Fourier transform mass spectrometer, we identified 627 phosphotyrosine sites mapping to 359 proteins. We observed alterations in the level of phosphorylation of 304 sites corresponding to 197 proteins upon curcumin treatment. We report here for the first time, curcumin-induced alterations in the phosphorylation of several kinases including TNK2, FRK, AXL, MAPK12 and phosphatases such as PTPN6, PTPRK, and INPPL1 among others. Pathway analysis revealed that the proteins differentially phosphorylated in response to curcumin are known to be involved in focal adhesion kinase signaling and actin cytoskeleton reorganization. Conclusions The study indicates that curcumin may regulate cellular processes such as proliferation and migration through perturbation of the focal adhesion kinase pathway. This is the first quantitative phosphoproteomics-based study demonstrating the signaling events that are altered in response to curcumin. Considering the importance of curcumin as an anti-cancer agent, this study will significantly improve the current knowledge of curcumin-mediated signaling in cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12014-016-9114-0) contains supplementary material, which is available to authorized users.
    Full-text · Article · Dec 2016
    • "Among them, curcumin is well known for its medicinal properties in Indian and Chinese medicine [18]. Its anti-cancer effects, among other numerous therapeutic effects, was reported mostly for breast cancer, prostate cancer and colon cancer [26][27][28], but the effects on choriocarcinoma cells had not been studied. The molecular targets of curcumin are diverse depending on cancer type, but effects are mediated primarily via the ERK1/2 and JNK MAPK pathways. "
    [Show abstract] [Hide abstract] ABSTRACT: Curcumin, a natural pigment for yellow color that originates from turmeric, is a diarylheptanoid widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant and anti-cancer effects on cells. In placental diseases including preeclampsia and preterm birth, curcumin reduces pro-inflammatory cytokines. Even though curcumin is regarded as a novel chemotherapeutic agent with strong apoptotic effects based on phenolic structure, little is known about its functional effects on choriocarcinoma. Therefore, in the present study, we investigated the chemotherapeutic effects of curcumin on choriocarcinoma cells (JAR and JEG3), which are valuable placental models. The results showed that curcumin decreased viability of choriocarcinoma cells in a dose-dependent manner. In addition, proliferative and migratory characteristics of JAR and JEG3 cells were inhibited by curcumin treatment and curcumin-induced apoptotic effects which were assessed using TUNEL and annexin V/propidium iodide (PI) staining. Moreover, curcumin decreased depolarization of mitochondrial membrane based on JC-1 staining and changed expression of apoptotic proteins. Phosphorylation of mitogen-activated protein kinases responsible for regulation of anti-cancer effects of curcumin were examined for dose- and time-dependent effects. The ERK1/2 and SAPK/JNK and their downstream molecules including P90RSK and c-Jun, respectively, were activated by curcumin. Moreover, pharmacological inhibitors of ERK1/2 (U0126) and SAPK/JNK (SP600125) suppressed ERK1/2 and SAPK/JNK activation respectively, and blockage of P38 MAPK by its inhibitor (SB203580) had a synergistic effect with curcumin. These results indicate that curcumin acts as a novel chemotherapeutic agent on human placental choriocarcinoma cells via activation of ERK1/2 and SAPK/JNK signal transduction cascades.
    Article · Aug 2016
    • "Curcumin was found to sensitize pancreatic cancer cells to gemcitabine in vitro [50]. It was published that it inhibits proliferation and induce apoptosis in LNCaP prostate cancer cells in vivo [51]. Curcumin inhibits dose-dependent the SSC4-oral cancer cells, LoVo-human colorectal cancer cells, K1-papillary thyroid cancer cells, KKU100, KKU-M156, KKU-M213 -human biliary cancer cells52535455. "
    [Show abstract] [Hide abstract] ABSTRACT: Curcuma longa Linnaeus and Zingiber officinale Roscoe are two main representatives of Zingiberaceae family studied for a wide range of therapeutic properties, including: antioxidant, anti-inflammatory, anti-angiogenic, antibacterial, analgesic, immunomodulatory, proapoptotic, anti-human immunodeficiency virus properties and anticancer effects. This study was aimed to analyse the ethanolic extracts of Curcuma rhizome (Curcuma longa Linnaeus) and Zingiber rhizome (Zingiber officinale Roscoe) in terms of polyphenols, antioxidant activity and anti-melanoma potential employing the B164A5 murine melanoma cell line. In order to evaluate the total content of polyphenols we used Folin-Ciocâlteu method. The antioxidant activity of the two ethanolic extracts was determined by DPPH assay, and for the control of antiproliferative effect it was used MTT proliferation assay, DAPI staining and Annexin-FITC-7AAD double staining test. Results showed increased polyphenols amount and antioxidant activity for Curcuma rhizome ethanolic extract. Moreover, 100 μg/ml of ethanolic plant extract from both vegetal products presented in a different manner an antiproliferative, respectively a proapoptotic effect on the selected cell line. The study concludes that Curcuma rhizome may be a promising natural source for active compounds against malignant melanoma.
    Full-text · Article · Jan 2015
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