Curcumin derivatives: Molecular basis of their anti-cancer activity

Abstract

Curcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of chemopreventive, anti-oxidant and anti-tumor properties. Although its promising chemotherapeutic activity, preclinical and clinical studies highlight Curcumin limited therapeutic application due to its instability in physiological conditions. To improve its stability and activity, many derivatives have been synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more stable than Curcumin in physiological medium. To explore the mechanism of their chemotherapeutic effect, we studied their role in proliferation in the HCT116 human colon cancer cells. We correlated kinetic stability and cellular uptake data to their biological effects. Both bDMC and DAC impair correct spindles formation and induce a p53-and p21 CIP1/WAF1 -independent mitotic arrest, which is more stable and long-lasting for bDMC. A subsequent p53/p21 CIP1/WAF1 -dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a consequence of the mitotic slippage, preventing postmitotic cells from re-entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct effect of the drug and concomitant to the mitotic block. Finally, we demonstrate that bDMC induces rapid DNA double-strand breaks, moving for its possible development in anti-cancer clinical applications.

Curcumin Stimulates Reactive Oxygen Species Production and Potentiates Apoptosis Induction by the Antitumor Drugs Arsenic Trioxide and Lonidamine in Human Myeloid Leukemia Cell Lines

“…Nonetheless, curcumin also may induce apoptosis in tumor cells, potentiate apoptosis induction by classical chemotherapeutic drugs, or both, supporting its potential use in anticancer therapies (Limtrakul, 2007;Reuter et al, 2008). In fact, in spite of its poor stability and bioavailability (Anand et al, 2007;Basile et al, 2009), the antitumor efficacy of curcumin has been proved in animal models and phase I clinical trials with multiple types of cancer (Anand et al, 2008). As with other plant-derived polyphenols, the proapoptotic action of curcumin has been largely attributed to the inhibition of defensive signaling pathways such as PI3K/ Akt and NF-B (Lin, 2007;Reuter et al, 2008), but other mechanisms may be equally important.…”

Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

“…It has previously been reported that curcumin has poor bioavailability in animal models and humans (28). This limitation has led researchers to generate a variety of synthetic analogues of curcumin, and investigate their capability to affect a number of molecular pathways implicated in tumorigenesis and cancer progression (29)(30)(31)(32). Typical structure modifications include the introduction of substituents on the phenyl rings and modifications of the length of the linker between the phenyl rings.…”

Nanotechnology: the word is new but the concept is old. An overview of the science and technology in food and food products at the nanoscale level

“…The polyphenolic compound curcumin is isolated from turmeric (Curcuma longa), a member of the ginger family, and has antioxidant (Ruby, Kuttan, Babu, Rajasekharan, & Kuttan, 1995), anti-inflammatory (Lantz, Chen, Solyom, Jolad, & Timmermann, 2005) and anti-cancer (Basile et al, 2009;Shi et al, 2006) properties. Curcumin's poor aqueous solubility, degradation and low bioavailability are obstacles for its uses in medicine (Basile et al, 2009). Camel β-casein micelles' ability to entrap curcumin was investigated, revealing that the micelle-curcumin interactions are mainly hydrophobic, critical to bioactive solubilisation ability, and ultimately its bioavailability and antioxidant activity (Esmaili et al, 2011).…”