Molecular Pathways Modulated by Curcumin Analogue, Diarylpentanoids in Cancer

While curcumin has a range of therapeutic benefits, its potent anticancer activity remains an attractive avenue for anticancer research owing to the multifactorial nature of cancer itself. The structure of curcumin has thus been used as a lead to design more potent analogues, and diarylpentanoids in particular have shown improved cytotoxicity over curcumin. Investigations of diarylpentanoids have demonstrated that these compounds exert anti-cancer effects through several signalling pathways that are associated with cancer. This review focuses on selected diarylpentanoids and highlights molecular targets that modulate key pathways involved in cancer such as NF-κB, MAPK/ERK, and STAT signalling. Future research will need to focus on drug interactions to explore potential synergistic actions of diarylpentanoids and further establish the use of diverse animal models.

[1]  D. Wolf,et al.  Curcumin: New Insights into an Ancient Ingredient against Cancer , 2019, International journal of molecular sciences.

[2]  A. Shafiee,et al.  Design and Synthesis of Curcumin-Like Diarylpentanoid Analogues as Potential Anticancer Agents. , 2016, Recent patents on anti-cancer drug discovery.

[3]  F. Izzo,et al.  Curcumin AntiCancer Studies in Pancreatic Cancer , 2016, Nutrients.

[4]  A. Kunnumakkara,et al.  Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far. , 2016, Recent patents on anti-cancer drug discovery.

[5]  L. Laino,et al.  Biological and therapeutic activities, and anticancer properties of curcumin. , 2015, Experimental and therapeutic medicine.

[6]  A. Barbieri,et al.  Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer , 2013, BioMed research international.

[7]  N. H. Nagoor,et al.  Alterations of MicroRNA Expression Patterns in Human Cervical Carcinoma Cells (Ca Ski) toward 1′S-1′-Acetoxychavicol Acetate and Cisplatin , 2013, Reproductive Sciences.

[8]  Aamir Ahmad,et al.  Perspectives on new synthetic curcumin analogs and their potential anticancer properties. , 2013, Current pharmaceutical design.

[9]  A. Conney,et al.  Synthesis and evaluation of curcumin-related compounds for anticancer activity. , 2012, European journal of medicinal chemistry.

[10]  J. Snyder,et al.  Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[11]  D. Mackenzie,et al.  The curcumin analog ca27 down‐regulates androgen receptor through an oxidative stress mediated mechanism in human prostate cancer cells , 2012, The Prostate.

[12]  J. Snyder,et al.  Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties. , 2012, International immunopharmacology.

[13]  B. Aggarwal,et al.  Multitargeting by curcumin as revealed by molecular interaction studies. , 2011, Natural product reports.

[14]  M. Mimeault,et al.  Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy , 2011, Chinese medicine.

[15]  Li Lin,et al.  Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030 , 2011, British Journal of Cancer.

[16]  B. Bao,et al.  Inactivation of AR/TMPRSS2-ERG/Wnt Signaling Networks Attenuates the Aggressive Behavior of Prostate Cancer Cells , 2011, Cancer Prevention Research.

[17]  H. Shibata,et al.  Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo , 2011, BMC pharmacology.

[18]  T. Carey,et al.  Sensitization of head and neck cancer to cisplatin through the use of a novel curcumin analog. , 2011, Archives of otolaryngology--head & neck surgery.

[19]  H. Shibata,et al.  Curcumin analog GO‐Y030 is a novel inhibitor of IKKβ that suppresses NF‐κB signaling and induces apoptosis , 2011, Cancer science.

[20]  Sahdeo Prasad,et al.  Turmeric, the golden spice: From traditional medicine to modern medicine , 2011 .

[21]  Li Lin,et al.  Two small molecule compounds, LLL12 and FLLL32, exhibit potent inhibitory activity on STAT3 in human rhabdomyosarcoma cells. , 2010, International journal of oncology.

[22]  J. Snyder,et al.  Activation of the p38 pathway by a novel monoketone curcumin analog, EF24, suggests a potential combination strategy. , 2010, Biochemical pharmacology.

[23]  Robert N. Taylor,et al.  Multiple Anticancer Activities of EF24, a Novel Curcumin Analog, on Human Ovarian Carcinoma Cells , 2010, Reproductive Sciences.

[24]  Li Lin,et al.  A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells , 2010, Molecular Cancer.

[25]  P. Limtrakul,et al.  The inhibitory effect of turmeric curcuminoids on matrix metalloproteinase-3 secretion in human invasive breast carcinoma cells , 2010, Archives of pharmacal research.

[26]  T. Kálai,et al.  Anticancer Efficacy of a Difluorodiarylidenyl Piperidone (HO-3867) in Human Ovarian Cancer Cells and Tumor Xenografts , 2010, Molecular Cancer Therapeutics.

[27]  T. Kálai,et al.  Safe and targeted anticancer efficacy of a novel class of antioxidant-conjugated difluorodiarylidenyl piperidones: differential cytotoxicity in healthy and cancer cells. , 2010, Free radical biology & medicine.

[28]  Pui-Kai Li,et al.  Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. , 2010, Cancer research.

[29]  J. Engelman,et al.  The PI3K pathway as drug target in human cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Serge Eifes,et al.  Curcumin―The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment , 2010, Toxins.

[31]  Li Lin,et al.  Curcumin analogue GO-Y030 inhibits STAT3 activity and cell growth in breast and pancreatic carcinomas. , 2009, International journal of oncology.

[32]  E. Wagner,et al.  Signal integration by JNK and p38 MAPK pathways in cancer development , 2009, Nature Reviews Cancer.

[33]  Li Lin,et al.  Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells , 2009, Anti-cancer drugs.

[34]  T. Kálai,et al.  Inhibition of Vascular Smooth-Muscle Cell Proliferation and Arterial Restenosis by HO-3867, a Novel Synthetic Curcuminoid, through Up-Regulation of PTEN Expression , 2009, Journal of Pharmacology and Experimental Therapeutics.

[35]  Jiayuh Lin,et al.  New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells , 2009, BMC Cancer.

[36]  S. Garbisa,et al.  Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. , 2009, The Journal of nutritional biochemistry.

[37]  Y. Li,et al.  Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. , 2009, Biomedical and environmental sciences : BES.

[38]  J. Snyder,et al.  Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin , 2008, Molecular Pharmacology.

[39]  K. Hideg,et al.  Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity. , 2008, Cancer research.

[40]  Stephen L. Abrams,et al.  Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia , 2008, Leukemia.

[41]  Robert A Newman,et al.  Bioavailability of curcumin: problems and promises. , 2007, Molecular pharmaceutics.

[42]  K. Hideg,et al.  EF24 Induces G2/M Arrest and Apoptosis in Cisplatin-resistant Human Ovarian Cancer Cells by Increasing PTEN Expression* , 2007, Journal of Biological Chemistry.

[43]  T. Tsai,et al.  Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[44]  P. Pantazis,et al.  Metabolism and Anticancer Activity of the Curcumin Analogue, Dimethoxycurcumin , 2007, Clinical Cancer Research.

[45]  H. Shibata,et al.  Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer , 2006, Molecular Cancer Therapeutics.

[46]  M. Metzler,et al.  Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver. , 2006, Journal of agricultural and food chemistry.

[47]  K. Ye PIKE/nuclear PI 3‐kinase signaling in preventing programmed cell death , 2005, Journal of cellular biochemistry.

[48]  B. Aggarwal,et al.  Curcumin‐induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B‐Raf/mitogen‐activated/extracellular signal‐regulated protein kinase pathway and the Akt pathway , 2005, Cancer.

[49]  A. Newton,et al.  PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. , 2005, Molecular cell.

[50]  D. Harrison,et al.  The JAK/STAT signaling pathway , 2004, Journal of Cell Science.

[51]  A. Dennison,et al.  Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration , 2004, British Journal of Cancer.

[52]  Nicola Gebbia,et al.  STAT proteins: From normal control of cellular events to tumorigenesis , 2003, Journal of cellular physiology.

[53]  T. Slaga,et al.  4-Hydroxy-3-methoxybenzoic acid methyl ester: a curcumin derivative targets Akt/NF kappa B cell survival signaling pathway: potential for prostate cancer management. , 2003, Neoplasia.

[54]  N. Chainani-Wu Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). , 2003, Journal of alternative and complementary medicine.

[55]  D. Aaronson,et al.  A Road Map for Those Who Don't Know JAK-STAT , 2002, Science.

[56]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[57]  T. Miyazawa,et al.  Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. , 2000, Life sciences.

[58]  A. Saraste,et al.  Morphologic and biochemical hallmarks of apoptosis. , 2000, Cardiovascular research.

[59]  L. Howells,et al.  Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex , 1999, Oncogene.

[60]  Chris Albanese,et al.  NF-κB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1 , 1999, Molecular and Cellular Biology.

[61]  Jen-kun Lin,et al.  Biotransformation of curcumin through reduction and glucuronidation in mice. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[62]  J. Cusack,et al.  Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB , 1999, Nature Medicine.

[63]  J. Duroux,et al.  Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships. , 1998, Cancer letters.

[64]  K. N. Rajasekharan,et al.  Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids. , 1996, Mutation research.

[65]  Y. Lazebnik,et al.  Nuclear events of apoptosis in vitro in cell-free mitotic extracts: a model system for analysis of the active phase of apoptosis , 1993, The Journal of cell biology.

[66]  Y. Oshika,et al.  P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo. , 1996, British Journal of Cancer.

[67]  P. Ramteke,et al.  Turmeric : the Golden Spice of Life , 2012 .

[68]  A. Olivera Inhibition of the NF-kappaB signaling pathway by the curcumin analogs, 3,5- Bis(2-pyridinylmethylidene)-4-piperidone (EF31) and 3,5-Bis(2- pyridinylmethylidene)-1-methyl-4-piperidone (UBS109): in-vitro and in-vivo studies , 2011 .

[69]  B. Aggarwal,et al.  Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. , 2009, The international journal of biochemistry & cell biology.

[70]  B. Aggarwal,et al.  Curcumin: the Indian solid gold. , 2007, Advances in experimental medicine and biology.

[71]  B. Aggarwal,et al.  Curcumin Derived from Turmeric ( Curcuma longa ): a Spice for All Seasons , 2005 .

[72]  Michael Karin,et al.  NF-kappaB in cancer: from innocent bystander to major culprit. , 2002, Nature reviews. Cancer.

[73]  Donald J L Jones,et al.  Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[74]  V. Ravindranath,et al.  Absorption and tissue distribution of curcumin in rats. , 1980, Toxicology.