Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines

Abstract

Abstract. Cdc42, a Rho GTPase family member, is involved in cell transformation, proliferation, survival, invasion and metastasis of human cancer cells. Overexpression of Cdc42 has been reported in several types of human cancer. However, the underlying mechanisms are not well understood. The present study showed that Cdc42 was overexpressed in 80 of 110 primary lung cancer patients, and overexpression of Cdc42 was significantly associated with high TNM stage and lymph node metastasis. Moreover, RNAi-mediated suppression of Cdc42 expression reduced actin filopodia formation, migration and invasion potential of a highly metastatic lung cancer cell line, 801D. In parallel, 801D cells were treated with curcumin and the effect on the expression of the Cdc42 gene at the transcriptional and translational levels was analyzed by RT-PCR and Western blotting. Curcumin inhibited cell migration, invasion and downregulated Cdc42 gene and Cdc42-related target gene expression in 801D cells. It also induced rearrangements of the actin cytoskeleton. These effects mimicked those of Cdc42 knockdown. Furthermore, xenograft experiments confirmed the suppression of tumor growth and invasion in vivo, which was due to the effect of curcumin and the inhibition of Cdc42 by curcumin. Our results showing the downregulation of Cdc42 expression by curcumin in lung cancer cells taken together with the clinical data suggest a potential therapeutic role for curcumin in inducing Cdc42-mediated inhibition of invasion of lung cancer cells.

MicroRNA-29a functions as a potential tumor suppressor through directly targeting CDC42 in non-small cell lung cancer

“…Consistent with its important functions in these distinct physiological and pathological processes, abnormal expression of CDC42 has been identified in numerous diseases, particularly in human cancer. CDC42 has been identified to be upregulated in a number of human cancers, including lung cancer (44). Therefore, it may be advantageous to investigate novel targeted therapy against CDC42 in lung cancer.…”

Unraveling the Anticancer Effect of Curcumin and Resveratrol

“…For instance, Chen and colleagues reported the effect of curcumin to prevent cancer progression and metastasis using an in vivo lung cancer model. In this work, it was demonstrated that curcumin downregulated the expression of Cdc42 and Rho GTPase protein that plays an important role in proliferation, invasion and metastasis [245]. In fact, several studies have associated the overexpression of Cdc42 and the progression of a variety of human cancers [246].…”

Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies

“…Overwhelmingly, mechanisms of action reported for the antitumor efficacy of curcumin in lung cancer cells are via mitochondrial-mediated cell death elicited by an increase in the Bax:B cell lymphoma-2 ratio or by an increase in intracellular reactive oxygen species (ROS) (Chanvorachote et al, 2009;Pongrakhananon et al, 2010;Saha et al, 2010;Wu et al, 2010;Wang et al, 2011Wang et al, , 2013bSahoo et al, 2012;Yang et al, 2012a,b;Liu et al, 2013;Xiao et al, 2013;Chen et al, 2014). Migration and invasive capacity of lung cancer cells may be further decreased by inhibition of matrix metalloprotease expression, decreased nuclear factor-kB, EGFR, Akt, signal transducer and activator of transcription 3, and Cdc42 signaling (Chen et al, 2004(Chen et al, , 2012Lee et al, 2005;Lin et al, 2009Lin et al, , 2012Puliyappadamba et al, 2010;Kaushik et al, 2012;Liu et al, 2013;Yamauchi et al, 2014;Zhou et al, 2013a;Li et al, 2014b). Although drug resistance in lung cancer is a primary cause for therapeutic failure, very few in vitro models of resistance have been used when investigating the potential of curcumin for tertiary interventional strategies.…”