Synergistic Role of Curcumin With Current Therapeutics in Colorectal Cancer: Minireview

Veterans Affairs Medical Center, Karmanos Cancer Institute, Department of Internal Medicine, Wayne State University, Detroit, Michigan 48201, USA.
Nutrition and Cancer (Impact Factor: 2.32). 11/2009; 61(6):842-6. DOI: 10.1080/01635580903285106
Source: PubMed


Despite the use of surgical resection and aggressive chemotherapy, nearly 50% of patients with colorectal carcinoma develop recurrent disease, highlighting the need for improved therapies. Curcumin (diferuloylmethane), the major active ingredient of turmeric (curcuma longa) with no discernable toxicity, has been shown to inhibit the growth of transformed cells and colon carcinogenesis at the initiation, promotion, and progression stages in carcinogen-induced rodent models. In a Phase I clinical trial, curcumin has been found to be extremely well tolerated and effective. In this review, we summarized the current status of our knowledge about the effectiveness of curcumin when given in combination with current chemotherapeutics such as 5-fluorouracil, oxaliplatin, and gemcitabine in treatment of gastrointestinal cancers with particular reference to colorectal cancer. Existing data suggest that curcumin in combination with chemotherapy is a superior strategy for treatment of gastrointestinal cancer.

Download full-text


Available from: Adhip P Majumdar, Oct 05, 2015
80 Reads
  • Source
    • "Our study provides evidence pleading for a potential new treatment strategy in lung cancer. Recent studies have described the potential usefulness of curcumin as adjuvant therapy in different types of cancer such as pancreatic, bladder or colorectal cancer (Kunnumakkara et al, 2007; Patel and Majumdar, 2009; Tharakan et al, 2010). Given our current data based on effects of curcumin–CD complexes on lung cancer development, one can hypothesise that curcumin could provide complementary effects to conventional therapeutics in order to reach maximum treatment efficiency in patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer. Methods: Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model. Results: Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin–CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin–CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects. Conclusion: Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy.
    British Journal of Cancer 08/2012; 107(7):1083-92. DOI:10.1038/bjc.2012.379 · 4.84 Impact Factor
  • Source
    • "Curcumin (diferuloylmethane) is a naturally occurring compound found in the plant Curcuma longa that has numerous medicinal properties including anti-inflammatory and antitumor effects [18-20]. Curcumin has been investigated extensively as a potential therapeutic agent for the treatment of many different cancers, such as colorectal carcinoma [21,22], head and neck squamous cell carcinoma [23], pancreatic cancer [24], and OSA [25,26]. Curcumin is known to target multiple biochemical pathways, such as those mediated by Wnt/β-catenin [26], NF-κB [20], growth factor receptors like EGFR and HER2 [27], and JAK/STAT [28] enhancing its effect on cancer cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells. Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT®), apoptosis (SensoLyte® Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting. Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway. These data demonstrate that the novel curcumin analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound in vivo.
    BMC Cancer 03/2011; 11(1):112. DOI:10.1186/1471-2407-11-112 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present work was to study the effect of the crude extract of Curcuma zedoaria on peripheral blood cells and tumor progression in C57Bl/6J mice injected with B16F10 murine melanoma cells. The intraperitoneal therapy showed a significant increase in total white and red blood cell counts, a decrease in peritoneal cell number and tumor volume reduction, whereas the oral administration revealed a noteworthy augmentation only in total leukocyte count. These results contribute to evaluate the importance of alternative treatments that employ phytotherapic compounds against tumor progression and its possible immunomodulation.
    Journal of Venomous Animals and Toxins including Tropical Diseases 01/2010; 16(2). DOI:10.1590/S1678-91992010000200013 · 0.80 Impact Factor
Show more