New Role of (−)-Epicatechin in Enhancing the Induction of Growth Inhibition and Apoptosis in Human Lung Cancer Cells by Curcumin

Abstract

Curcumin, a phenolic compound isolated from the plant Curcuma longa (Linn), is ingested every day in the Indian subcontinent and is well reported to possess cancer-preventive activity. To achieve effective cancer prevention with curcumin, we need to find a new method to enhance the effects of curcumin in the diet. Based on our evidence that (−)-epicatechin (EC), an inert catechin, enhances the cancer-preventive activity of green tea catechins, we studied the enhancing effects of EC on inductions of growth inhibition and apoptosis in human lung cancer cell lines PC-9 and A549 with curcumin. The combination of curcumin with EC significantly increased the inhibition of cell growth compared with curcumin or EC alone. The combination similarly increased both apoptosis and expression of GADD153 and GADD45 genes, associated with their enhanced protein production. Knockdown of GADD153 or GADD45 by small interfering RNA abrogated the apoptosis induction and growth inhibition induced by the combination, indicating the crucial role of their upregulation. Treatments of PC-9 cells with c-Jun-NH 2 -kinase inhibitor SP600125, with p38 mitogen-activated protein kinase inhibitor SB202190 and with PD98059 (extracellular signalregulated kinase 1/2 inhibitor) all increased the upregulation of GADD153 and GADD45 genes by the combination. Because EC was previously shown to enhance the incorporation of EGCG into PC-9 cells, we think that EC has similar effects on curcumin. This report is the first report on the enhancing effects of EC on curcumin, and the data suggest that EC plays a significant role in the enhancement of the cancerpreventive activity of curcumin in the diet. Cancer Prev Res; 3(8); 953-62. ©2010 AACR.

Health Benefits of Phenolic Compounds Against Cancers

“…cells [48]. Hexameric procyanidins inhibited the deoxycholic acid (DOC)-induced cytotoxicity and partly delayed the DOC-induced Caco-2 cell apoptosis [49].…”

Jaceosidin inhibits proliferation of human bladder cancer T24 cells through induction of cell cycle arrest and apoptosis

“…The regulation of apoptosis is, therefore, the most important in the treatment of cancer (Fulda, 2010;Lawen, 2003;Reed, 2002). Accumulated evidences indicated that the most of chemotherapeutic agents halt tumor cells proliferation via induction of apoptosis (Saha et al, 2010;Wu et al, 2009;Zhang, 2002). We examined whether jaceosidin inhibited cell growth of T24 cells through the induction of apoptosis.…”

Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells

“…Although several reports have shown that EGCG exerts its anticancer activity by targeting specific cell signaling pathways, the underlying mechanism is not yet fully understood. Previous reports revealed that EGCG treatment induces lung cancer cell apoptosis or cell cycle arrest (18,35). Other groups also found that the tumor suppressor gene p53 may be involved in the antitumor activity of EGCG since cancer cells expressing wild-type p53 are more sensitive to EGCG treatment compared with p53-null or p53 knock down cancer cells (36,40).…”

“…(-)-Epigallocatechin gallate (EGCG), a type of polyphenol, which is the most well known, abundant and active compound found in green tea, exerts its anticancer effects in a wide range of malignancies (2,7). Previous studies have suggested that multiple signaling pathways and mechanisms are involved in the antitumor activity of EGCG (1,(8)(9)(10), including suppression of various protein kinases (11)(12)(13); disruption of the activation of transcription factors such as EGFR, NF-κB, AP-1 and STATs (14)(15)(16); induction of cell cycle arrest or apoptosis (17,18); and inhibition of cell migration and metastasis (19)(20)(21)(22)(23)(24).…”