Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1

Li, Jun; Khan, Md. Asaduzzaman; Wei, Chunli; Cheng, Jingliang; Chen, Hanchun; Yang, Lisha; Ijaz, Iqra; Fu, Junjiang

doi:10.3390/molecules22122105

Cited by 55 publications

(47 citation statements)

References 40 publications

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“…Tq has been shown to inhibit cancer metastasis by down regulating the TWIST1 protein (Khan et al, ). Another study proves Tq to effectively inhibit cervical cancer cells by key regulatory proteins like Twist1/E‐Cadherin/EMT and/or Zeb1/E‐Cadherin/EMT (Li et al, ). In this study, we mimicked the cancer cell migration in the trans‐endothelial cell migration assay.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

Dera

Rajagopalan

2019

J Food Biochem

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Thymoquinone (Tq) is an active compound from Nigella sativa which is used in traditional medicine. The effect of Tq on kidney cancer and the pathway of action remain unproven. Herein, we report the anticancer properties of Tq on kidney cancer cells. Tq demonstrated anti‐proliferative effects in A498 cells with a GI50 value of 40.07 µM and Caki‐1 cells with a GI50 of 51.04 µM by the MTT assay. Tq exhibited nuclear fragmentation and inhibited trans‐endothelial migration of A498 and Caki‐1 cells in a dose‐responsive manner. Time‐dependent increase in Annexin V‐positive cells and sub‐G0/G1 cell population was observed post‐Tq treatment. The compound increased Bax protein levels and reduced Bcl‐2 protein levels dose dependently in cells, thereby favoring apoptosis. Tq decreased the phosphorylation of Akt in both kidney cell types. The results suggest effective anticancer activity of Tq on kidney cancer cells which may be mediated by the Akt pathway. Practical applications Results from the current investigation will through more light on the mechanistic pathway of Tq activity on the inhibition of kidney cancer cell proliferation. The output of this preclinical in vitro study may be translated into better chemotherapeutics of Tq and its analogs to treat kidney cancer. However, a detailed investigation on in vivo models is recommended.

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Section: Discussionmentioning

confidence: 99%

Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

Dera

Rajagopalan

2019

J Food Biochem

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“…Therefore, TQ has been regarded as a promising agent for numerous diseases. Previous studies have revealed that TQ may exhibit high anti‐tumor efficiency against various cancers, such as breast cancer, gastric cancer, cervical cancer, colon cancer, central nervous system cancer, ovarian cancer, prostate cancer, bladder cancer and renal cell cancer . It is well known that invasion and metastasis play vital roles in the progression of tumors.…”

Section: Introductionmentioning

confidence: 99%

“…Recent research has shown that TQ can inhibit metastasis and EMT in prostate cancer via the transforming growth factor‐beta/Smad2/3 signaling pathway . Jun Li and his team also indicated that TQ inhibited the migration and invasion abilities in cervical cancer cells, which might be regulated via the expression of Twist1, Zeb1 and E‐cadherin directly . However, there are few studies that consider the effect of TQ on metastasis in renal cell cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have revealed that TQ may exhibit high anti-tumor efficiency against various cancers, such as breast cancer, gastric cancer, cervical cancer, colon cancer, central nervous system cancer, ovarian cancer, prostate cancer, bladder cancer and renal cell cancer. [10][11][12][13][14][15][16][17][18] It is well known that invasion and metastasis play vital roles in the progression of tumors. Recent research has shown that TQ can inhibit metastasis and EMT in prostate cancer via the transforming growth factor-beta/Smad2/3 signaling pathway.…”

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confidence: 99%

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Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

et al. 2018

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Thymoquinone (TQ, 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti‐tumor efficiency in various cancers. Autophagy is a self‐digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786‐O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ‐treated RCC cells, and then found that autophagy was induced by TQ in 786‐O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy‐dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ‐induced autophagy in RCC treatment.

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“…91 Thymoquinone, which is a compound derived from the black seeds of a Middle Eastern flower called Nigella sativa, could inhibit the migration and invasion of cervical cancer cells, likely via Twist1 and/or ZEB1/E-cadherin/ EMT. 92 In ovarian cancer, recent data showed that ginsenoside Rb1 may reverse hypoxia-induced EMT by abrogating the suppressive effects of miR-25 on EP300 and E-cadherin. 93 In addition, ginsenoside Rg3 was verified to increase sensitivity to cisplatin by inhibiting NF-κBinduced EMT and stemness in hypoxic lung cancer cells.…”

Section: Medicine and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Traditional Chinese medicine as targeted treatment for epithelial‐mesenchymal transition‐induced cancer progression

Liu

Fei

Cheng

et al. 2018

J of Cellular Biochemistry

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The epithelial‐mesenchymal transition (EMT) program, which loosens cell‐cell adhesion complexes, endows cells with enhanced migratory and invasive properties. Furthermore, this process facilitates both the development of drug resistance and immunosuppression by tumor cells, which preclude the successful treatment of cancer. Recent research has demonstrated that many signaling pathways are involved in EMT progression. In addition, cancer stem cells (CSCs), vasculogenic mimicry (VM) and the tumor‐related immune microenvironment all play important roles in tumor formation. However, there are few reports on the relationships between EMT and these factors. In addition, in recent years, traditional Chinese medicine (TCM) has developed a unique system for treating cancer. In this review, we summarize the crucial signaling pathways associated with the EMT process in cancer patients and discuss the interconnections between EMT and other molecular factors (such as CSCs, VM, and the tumor‐related immune microenvironment). We attempt to identify common regulators that might be potential therapeutic targets to thereby optimize tumor treatment. In addition, we outline recent research on TCM approaches that target EMT and thereby provide a foundation for further research on the exact mechanisms by which TCMs affect EMT in cancer.

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Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1

Cited by 55 publications

References 40 publications

Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

Traditional Chinese medicine as targeted treatment for epithelial‐mesenchymal transition‐induced cancer progression

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