Inhibition of NF-[kappa]B and metastasis in irinotecan (CPT-11)-resistant LoVo colon cancer cells by thymoquinone via JNK and p38

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-[kappa]B 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/IKK[alpha]/[beta]/NF-[kappa]B pathway. TQ resulted in reduced total and phosphorylation of IKK[alpha]/[beta] and NF-[kappa]B 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-[kappa]B 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.