Main Article Content
Colorectal cancer (CRC) is one of the most common types of cancer seen in the world. 5-Fluorouracil (5-Fu) plus Oxaliplatin (1-OHP) remains the backbone of CRC chemotherapeutics, but with limited success. Phenoxodiol (Pxd) is an isoflavone analog with antitumor activity against various types of cancers, and sensitizes chemoresistant cancer cells to chemotherapeutics including platinum and taxanes. This study was, therefore, undertaken to examine whether Pxd pre-treatment with conventional chemotherapeutic agent(s) 5-Fu and 1-OHP co-administration be a therapeutic strategy for CRC. Cell viability and cytotoxicity were evaluated using dimethyl-thiazolyl diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase assays. The percentage of apoptotic and necrotic cells were determined by fluorescence microscopy analysis. Besides, active Caspase-3 levels by ELISA and relative mRNA levels of Caspase 3 (CASP3), CASP8 and CASP9 genes were determined by quantitative real-time PCR (qPCR) analysis. The pre-treatment of Pxd followed by 5-Fu and 1-OHP co-administration was more effective at inhibiting cell viability than either chemotherapeutic agents treatment alone. When compared to 5-Fu with 1-OHP alone treatment, Pxd pre-treatment overwhelmingly increased apoptotic Caspase-3 activity levels in CRC cells. Moreover, qPCR analyses showed that CASP3 and CASP9 mRNA levels significantly increased after pre-treatment with Pxd followed by 5-Fu and 1-OHP treatments, compared to 5-Fu with 1-OHP alone. Our results suggested that Pxd enhanced the in vitro antitumor activity of 5-Fu and 1-OHP. Our study also suggested that Pxd may be a potential candidate agent in advanced CRC and inclusion of Pxd to the conventional chemotherapeutic agent(s) could be an effective therapeutic strategy for CRC.
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).