MJ-33 (2-(3-ethoxyphenyl)-6-pyrrolidinylquinazolinone)-induced cell autophagy and apoptosis in 5-fluorouracil (5FU)-resistance HT-29 colorectal cancer cells

Drug resistance is one of the most difficulty that need to overcome during cancer treatment. 5-FU is the first-line drug, using in monotherapy or in combination with other chemotherapies to treat CRC. However, about 50% of patients with metastatic CRC are resistant to  5-FU-based chemotherapies. Therefore, the development of new therapy for 5-FU-resistant CRC is highly desirable.
    Apoptosis inactivation was commonly found in chemotherapy-resistant cells, thus, therapeutic approach of apoptosis re-activation or autophagic cell death promotion maybe useful. MJ-33 is a quinazolinone derivative, designed and synthesized in our lab. The anti-metastasis activity of MJ-33 in prostate cancer cells was first published in 2011. However, no study on MJ-33 in chemotherapy-resistant cells have been reported. In this study, we investigate the anti-cancer activity of MJ-33 in HT29/5FUR - a well established 5-FU-acquired resistant cell line. We hypothesize that the mechanism of MJ-33-induced anti-cancer activity is associated with the mechanism of apoptosis and autophagy.
Research Methods: Viability assay; Kinetic cell confluence assay; Morphology observation; Immunofluorescence staining; Western blotting
Our results revealed that, MJ-33 inhibits proliferation, induces apoptosis and autophagy in HT29/5FUR cells in vitro.  MJ-33-induced apoptosis was regulated via caspase-dependent pathway. MJ-33 was found as a potential new chemotherapeutic adjuvant, for treating 5-FU-resistant CRC.