Thymoquinone inhibits metastatic phenotype and epithelial‑mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway

Abstract

Thymoquinone, isolated from the seeds of Nigella sativa, has exhibited antitumor properties in a variety of cancer types. However, few studies have investigated the effect of thymoquinone (TQ) on migration and invasion in renal cell carcinoma (RCC). In the present study, our results confirmed that TQ significantly inhibited the migration and invasion of the human RCC 769‑P and 786‑O cell lines, as demonstrated by wound healing and Transwell assays. Additionally, TQ upregulated the expression of E‑cadherin and downregulated the expression of Snail, ZEB1 and vimentin at the mRNA and protein levels in a concentration‑dependent manner. Subsequently, the phosphorylation levels of liver kinase B1 (LKB1) and AMP‑activated protein kinase (AMPK) were increased upon TQ treatment. To further validate the role of LKB1/AMPK signaling, we revealed that TQ‑mediated increase of E‑cadherin level and reduction of Snail level could be further enhanced by LKB1 overexpression. Furthermore, co‑treatment with the AMPK inhibitor Compound C attenuated the anti‑metastatic effect of TQ on RCC and partially abrogated the high expression of E‑cadherin and the low expression of Snail mediated by TQ. In contrast, the AMPK activator AICAR demonstrated the opposite effect. Collectively, the present study revealed that TQ could markedly suppress the metastatic phenotype and reverse the epithelial‑mesenchymal transition in RCC by regulating the LKB1/AMPK signaling pathway, indicating that TQ may be a potential therapeutic candidate against RCC.

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

“…A concentration-dependent enhancement in phosphorylation of LKB1 and AMPK was shown over 24 hr TQ treatment in 786-O cells. Upregulation in the expression of LKB1 enhanced the E-cadherin expression and reduces the Snail expression upon thymoquinone treatment in 786-O and 769-P cells (Chen et al, 2017, Kou et al, 2018).…”

“…The migration of 769-P and 786-O cells significantly diminished and treatment of TQ with 10 uM for 24 hr significantly reduced the invasiveness of 769-P and 786-O cells. LKB1/AMPK signalling is required for the cancer metastasis and a concentration-dependent TQ treatment increases the phosphorylation level of both LKB1 and AMPK upon in both the cancer cell lines (Kou et al, 2018).…”

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/β-Catenin Pathway in a Murine Model of Lupus Nephritis

“…EMT plays an important role in the progression of TIL in human LN (54, 55). EMT is a pathologic process wherein epithelial cells transdifferentiate into motile mesenchymal cells after kidney damage.…”

<p>Oridonin Induces Apoptosis of Laryngeal Carcinoma via Endoplasmic Reticulum Stress</p>

“…It was performed as previously mentioned. 11 Briefly, laryngeal carcinoma Hep-2 and TU212 cells were harvested after oridonin treatment, and the protein lysates were extracted by RIPA Cell Lysis Buffer. Then, the cell lysates were centrifuged at 12,000 g at 4°C for 15 min.…”

“…It was conducted as previously mentioned. 11 CHOP cDNA was cloned into pcDNA3.1 vector. After laryngeal carcinoma Hep-2 or TU212 cells reached 80% confluency for plasmid transfection, then the cells were transiently transfected with X-tremeGENE HP DNA Transfection Reagent (Roche, Switzerland) following the manufacturer’s instructions, and prepared for the subsequent experiments.…”