Inhibition of NF‐κB and metastasis in irinotecan (CPT‐11)‐resistant LoVo colon cancer cells by thymoquinone via JNK and p38

Abstract

Clinically used chemotherapeutics can effectively eliminate most tumor cells. However, they cause unwanted side effects and result in chemoresistance. To overcome such problems, phytochemicals are now used to treat cancers by means of targeted therapy. Thymoquinone (TQ) is used to treat different cancers (including colon cancer) and is an NF-κB inhibitor. Irinotecan resistant (CPT-11-R) LoVo colon cancer cell line was previous constructed by step-wise CPT-11 challenges to un-treated parental LoVo cells and expresses EGFR/IKKα/β/NF-κB pathway. TQ resulted in reduced total and phosphorylation of IKKα/β and NF-κB and decreased metastasis in CPT-11-R cells. TQ not only reduced activity of ERK1/2 and PI3K but also activated JNK and p38. Furthermore, TQ was also found to suppress metastasis through activation of JNK and p38. Therefore, TQ suppressed metastasis through NF-κB inhibition and activation of JNK and p38 in CPT-11-R LoVo colon cancer cells. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 669-678, 2017.

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

“…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.…”

“…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.…”

Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma

“…This activation results in increased cytotoxicity and improved antitumor response in human tumor xenograft models of NB 10 . Irinotecan is currently being used in front-line treatment for NB and tested in combination with other drugs in a phase I clinical trial for this disease, 11 as well as colon cancer 12, 13. Clinical trials with this agent are also under way in variety of other solid malignancies (e.g., sarcomas and non-small-cell lung cancer) 14, 15, 16, 17, 18…”

Treatment mechanism of matrine in combination with irinotecan for colon cancer

“…At present, CPT-11 is used as the first-line chemotherapy drug for patients with colorectal cancer, but patients usually experience serious adverse effects including delayed diarrhea. Thus, clinical applications of CPT-11 are limited (5). Matrine (MA) is a natural compound extracted from root of Sophora flavescens with a wide range of pharmacological activities including anti-hepatic fibrosis, anti-viral, anti-arrhythmic, anti-inflammation and anti-tumor (6).…”