Tetrahydrocurcumin‑induced autophagy via suppression of PI3K/Akt/mTOR in non‑small cell lung carcinoma cells

Abstract

Lung carcinoma is the leading cause of mortality due to cancer worldwide. Autophagy has a significant role in the development and progression of non‑small cell lung carcinoma (NSCLC). A previous study has revealed that tetrahydrocurcumin (THC), a traditional Chinese medicine isolated from Curcuma wenyujin (Chen & Ling, 1981), induces autophagy in human A549 NSCLC cells. The present study evaluated THC‑induced autophagy in A549 cells using various assays, including the Cell Counting Kit‑8, acridine orange staining, flow cytometry, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and western blot analysis of the markers of autophagy. THC inhibited the growth and proliferation of A549 cells (P<0.05). Acridine orange staining and flow cytometry revealed that THC treatment significantly enhanced autophagic cell proliferation inhibition (P<0.05). The RT‑qPCR analysis revealed that THC treatment increased Beclin‑1 expression level and compared with the control group (P<0.05). The light chain 3 (LC3)‑II/LC3‑I ratio was reduced in THC‑treated cells when compared with the control group (P<0.05). Protein expression of various markers of autophagy, including p62, phosphorylated (p)‑mechanistic target of rapamycin (mTOR), phosphoinositide 3‑kinase (PI3K), p‑PI3K, protein kinase B (Akt), and p‑Akt was significantly reduced in THC‑treated cells (P<0.05). In conclusion, the present study revealed the underlying mechanisms associated with THC‑induced autophagy. A promising method of enhancing the therapeutic efficacy of THC against NSCLC cells may include inducing autophagy via inhibition of the PI3K/Akt/mTOR signaling pathway.

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

“…Several studies have investigated the efficacy of curcumin and THC in cancer treatment (Aggarwal et al, ; Oh et al, ; Song et al, ; Wu et al, ; Wu et al, ). A study indicated that both curcumin and THC can inhibit the function of P‐glycoprotein, a drug transporter linked to multidrug resistance, and significantly increase the sensitivity of cancer cells to vinblastine, mitoxantrone, and etoposide (Limtrakul, Chearwae, Shukla, Phisalphong, & Ambudkar, ).…”

“…THC induces HL60 cell autophagy through the coordinative modulation of PI3K/Akt‐mTOR and MAPK signaling pathways (Song et al, ). R‐HL60 cells were treated with THC for 24 hr with or without pretreatment with autophagy inhibitor (3‐methyladenine, 3‐MA); subsequently, AO fluorescence was detected through flow cytometry.…”

Reductive metabolites of curcumin and their therapeutic effects

“…THC showed lower inhibitory activity against inflammation-associated carcinogenesis in mice [ 79 ]. THC, as a known antitumor compound [ 72 ], induced autophagy that was found associated with the suppression of PI3K/Akt/mTOR signaling in A549 lung cancer cells [ 73 ]. THC inhibited human breast cancer MCF-7 cell proliferation.…”

The Cancer Chemopreventive and Therapeutic Potential of Tetrahydrocurcumin

“…The autophagy-inducing effect of tetrahydrocurcumin was also found in non-small-cell lung carcinoma cells. Treatment of A549 lung cancer cells with tetrahydrocurcumin resulted in autophagic cell death through an increase in the LC3 I/II ratio and Beclin-1 while in parallel downregulating PI3K/Akt/mTOR signaling [ 82 ].…”