Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549

Abstract

To investigate the anticancer effects of curcumin-induced autophagy and its effects on the human lung adenocarcinoma A549 cell line, inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT assay was used to measure cell viability. Autophagy was detected using acridine orange (AO) staining and 3-methyladenine (3-MA) was used as an autophagy-specific inhibitor. Dose- and time-dependent A549 cell viability inhibition was observed following curcumin treatment. A dose-dependent increase in the red fluorescent structures in A549 cells was identified following curcumin treatment for 48 h through AO staining. In addition, the activation of autophagy was determined through changes in the number of autophagic vesicles (AVs; fluorescent particles) infected with monodansylcadaverine (MDC). The fluorescence intensity and density of AVs in the curcumin-treated groups were higher at 48 h compared with the control group. Finally, the MTT assay demonstrated that the survival rates of the curcumin-treated cells were increased when pretreated with 3-MA for 3 h, indicating that the inhibitory effect of curcumin on A549 cells is reduced following the inhibition of autophagy. Furthermore, AO and MDC staining confirmed that 3-MA does inhibit the induction of autophagy. Thus, it was hypothesized that the induction of autophagy is partially involved in the reduction of cell viability observed following curcumin treatment. The anticancer effects of curcumin on A549 cells can be reduced using autophagy inhibitors. This suggests a possible cancer therapeutic application of curcumin through the activation of autophagy. These findings have improved the understanding of the mechanism underlying the anticancer property of curcumin.

Transcriptional Activation of Human GD3 Synthase (hST8Sia I) Gene In curcumin-Induced Autophagy in A549 Human Lung Carcinoma Cells

“…In the present study, we found that curcumin induced autophagy in A549 cells, as evidenced by immunofluorescence staining of LC3. Our finding is in agreement with previous studies [19,20] demonstrating autophagy induction by curcumin in A549 cells. At the same time, we also found that gene expression of hST8Sia I catalyzing ganglioside GD3 synthesis was significantly increased by curcumin treatment in A549 cells.…”

“…Recent studies demonstrated that curcumin also induces autophagy in various types of cancer cells, such as malignant gliomas [9] prostate cancer [10], breast cancer [11], osteosarcoma [12], gastric cancer [13], oral squamous cell carcinoma [14], uterine leiomyosarcoma [15], leukemia [16], and colon cancer [17,18]. In addition, it has also been recently reported that curcumin triggers autophagy in human lung adenocarcinoma cells [19,20].…”

Mechanistic Understanding of Curcumin’s Therapeutic Effects in Lung Cancer

“…Curcumin was shown to inhibit PI3K/Akt/mTOR pathways in NSCLC cells A549 [118] and H1299 [119]. The findings demonstrated that curcumin treatment suppresses the PI3K/Akt/mTOR pathway by decreasing the Akt and mTOR phosphorylation thus inducing apoptosis [119,120]. On a different note, a tumor suppressor phosphatase and tensin homolog (PTEN) protein has been found to inactivate PI3K/Akt/mTOR pathways through dephosphorylation of PIP 3 to PIP 2 [121].…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Curcumin is shown to induce anti-cancer activities through the disruption of mitochondrial membrane potential and blockade at G2/M phase of the cell cycle in human epidermoid carcinoma A-431 cells [47]. In addition, mammalian target of rapamycin (mTOR) plays a vital role in curcumininduced autophagy and apoptosis [30,[48][49][50]. Curcumin induces apoptosis and autophagy through the inhibition of phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway in human NSCLC A549 cells [30], while it induces autophagy by reducing Akt phosphorylation and mTOR in human melanoma A375 and C8161 cells [49].…”