Annelyse Duvoix

Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition

Expression of glutathione S-transferase P1-1 (GSTP1-1) is correlated to carcinogenesis and resistance of cancer cells against chemotherapeutic agents. Curcumin, a natural compound extracted from Curcuma longa, has shown strong antioxidant and anticancer properties and also the ability to regulate a wide variety of genes that require activating protein 1 and nuclear factor kappaB (NF-kappaB) activation. In the present study, we examined the inhibitory effect of curcumin on the expression of GSTP1-1 mRNA as well as protein, and we correlated this inhibition with the apoptotic effect of curcumin on K562 leukemia cells. Curcumin efficiently inhibited the tumour necrosis factor alpha- and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter activity was also inhibited by curcumin as shown by reporter gene assay. In parallel, curcumin induced pro-caspases 8 and 9 as well as poly ADP ribose polymerase cleavage and thus leading to apoptosis in K562 cells. Our results overall add a novel role for curcumin as this chemoprotective compound could contribute to induce apoptosis by its ability to inhibit the GSTP1-1 expression at the level of transcription.

An introduction to the molecular mechanisms of apoptosis.

Abstract: Apoptosis is a type of cell death that has been observed and studied for more than a century. The process of apoptosis was described as “programmed cell death” in 1964, and the term apoptosis, from a Greek word meaning “to fall away from” and describing the fall of dead leaves from trees in autumn, was only coined in 1972. During the last 30 years, this type of cell death has been extensively investigated and the molecular mechanisms underlying this cell suicide well characterized. Apoptosis is a physiological phenomenon necessary to tissue and body genesis and homeostasis, but defects in its regulation may cause numerous diseases, including cancer. Investigating the mechanisms of apoptosis is thus important to discover new cellular regulators that could be potential targets for new death‐inducing drugs.

Curcumin-Induced Cell Death in Two Leukemia Cell Lines: K562 and Jurkat

Abstract: Curcumin presents strong antioxidant and anticancer properties. However, molecular mechanisms leading to curcumin‐induced cell death are poorly understood. The effect of curcumin was compared in two different leukemia cell lines: K562 and Jurkat. Cell death was induced in both cell lines, and apoptosis pathways were investigated by Western blot analysis. Decreases in pro‐caspase 8 and 9 levels were observed. BH3 interacting domain death agonist (Bid) was also cleaved. Jurkat cells appeared to be more sensitive to curcumin, and apoptosis takes place earlier.

Gene expression profiling related to anti-inflammatory properties of curcumin in K562 leukemia cells.

A strong relationship exists between inflammation and carcinogenesis. To bring insights into the anti‐inflammatory mechanisms by which chemopreventive agents, such as curcumin, are able to counteract the action of inflammation mediators, such as tumor necrosis factor‐α (TNF‐α), we compared gene expression profiles in K562 cells treated with curcumin‐TNF‐α versus TNF‐α alone. Microarray data analysis revealed that, among the 376 differentially expressed genes by curcumin treatment, genes belonging to the cell cycle and the Janus kinase‐signal transducer and activator of transcription signaling pathways were downregulated. This study also indicated that the upregulation of the heat shock family genes is highly implicated in the anti‐inflammatory effect of curcumin.

Curcumin Stability and Its Effect on Glutathione S-Transferase P1-1 mRNA Expression in K562 Cells

Abstract: To investigate the stability of curcumin in physiological media, the absorption variation of a curcumin solution was measured in 0.1% and 10% FCS. Under daylight conditions, curcumin degraded very rapidly in 0.1% FCS and was found to be more stable in higher serum concentrations. Under dark conditions, almost no decomposition could be observed after 2 h, whether the measurements were performed in 0.1% or 10% FCS. Furthermore, depending on the medium concentration, differential glutathione S‐transferase P1‐1 mRNA expression could be observed in K562 cells after incubation with curcumin. Indeed, incubation in 0.1% FCS led to a decrease of mRNA expression, whereas incubation in 10% FCS induced an increase of mRNA production.