Contents

Search

curcumin (Theracurmin)

A compound with antioxidant properties derived from extracts of turmeric (Curcuma longa) & curry. Classification: Classified as a diferuloylmethane. Function: Effect on apoptosis & interaction with chemotherapeutic agents is variable [2,7] Curcumin inhibits: 1) cell proliferation a) various tumor cell lines -> breast, prostate, squamous carcinoma b) Helicobacter pylori [2] 2) cyclin D1 via transcriptional & post-transcriptional mechanisms [1] 3) CDK4 mediated phosphorylation of Rb protein 4) TNF-alpha induced COX2 gene transcription 5) NF kappa B activation a) PMA activation of NF kappa B & AP1 b) TNF-alpha induced nuclear translocation & DNA binding of NF kappa B 6) catalytic activity of epidermal ERK1/ERK2 7) aminopeptidase N, an enzyme that promotes angiogenesis & facilitates tumor invasiveness 8) src & focal adhesion kinase [5] 9) ubiquitin-proteasome system [8] 10) glutathione S-transferase P [9] 11) telomerase reverse transcriptase [10] 12) cyclooxygenase-2 [11] 13) sarcoplasmic/endoplasmic reticulum Ca+2 ATPase [13] Curcumin induces: 1) apoptosis through mitochondrial pathway [8] 2) heme oxygenase-1 [6a,b] -> via Nrf2 & the antioxidant response element [6] Pharmacology: - antioxidant with anti-inflammatory properties - in a single trial, curcumin benefit for major depression not statistically significant [15,16]* - Theracurmin may lead to improved memory & attention in non-demented adults [14] - benefits associated with decreases in amyloid & tau accumulation in brain regions modulating mood & memory [14] * GRS9 concludes curcumin may help with depression [16] Dosage: - 90 mg PO BID (as Theracurmin) [14] Pharmacokinetics: - curcumin is reduced to tetrahydrocurcumin in the GI tract - curcumin & tetrahydrocurcumin are poorly absorbed from the GI tract - measurable serum levels from oral intake may be difficult to achieve Adverse effects: Toxicity: -> a mM concentrations, curcumin is neurotoxic in vitro -> low affinity binding to ATP binding sites of kinases proposed

General

alkene; olefin ketone phenol

Database Correlations

PUBCHEM correlations

References

  1. Mukhopadhyay A et al Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4- mediated retinoblastoma protein phosphorylation. Oncogene 21(57):8852-61, 2002 PMID: 12483537
  2. Deeb D et al Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2:95-103, 2003 PMID: 12533677
  3. Chemical & Engineering News, Sept 1, 2003, pg 8 Chem Biol 10:695, 2003
  4. Nature Reviews Cancer 2003
  5. Leu T et al Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity. Biochen Pharmacol 11:1475, 2003 PMID: 14637190
  6. Scapagnini G et al Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 61:554, 2002 PMID: 11854435 - Balogun E et al Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371(pt 3):887, 2003 PMID: 12570874
  7. Bharti AC et al Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101:1053, 2002 PMID: 12393461 - Somasundaram S et al Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62:3868, 2002 PMID: 12097302
  8. Jana NR et al Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway. J Biol Chem (Epub) 2004 PMID: 14701837
  9. Duvoix A et al Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition. Biochem Pharmacol 66:1475, 2003 PMID: 14555224
  10. Ramachandran C et al Scientific World Journal 1:1(1 Suppl 3): 109, 2002
  11. Shishodia S et al Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24:1269, 2003 PMID: 12807725
  12. Mahady GB et al Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 22(6C):4179, 2002 PMID: 12553052
  13. Egan ME et al Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600, 2004 PMID: 15105504
  14. Small GW, Siddarth P, Li Z et al Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. American Journal of Geriatric Psychiatry. 2017 http://www.ajgponline.org/article/S1064-7481(17)30511-0/fulltext
  15. Sanmukhani J, Satodia V, Trivedi et al Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014 Apr;28(4):579-85. PMID: 23832433
  16. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016