Revista de Farmacologia Clínica e Experimental

Abstrato

Synergistic Anti-proliferative Effects of Cucurbitacin I and Irinotecan on Human Colorectal Cancer Cell Lines

Eyol E,Tanrıverdi Z,Karakuş F,Yılmaz K,Ünüvar S*

Colorectal cancer is the third most common cancer in men and the second in women worldwide. Treatments used for colorectal cancer include some combinations of chemotherapy, radiation therapy, surgery and targeted therapy to increase survival rates of cancer patients and decrease mortality caused by colorectal cancer. One of the many common chemotherapy drugs used in metastatic and recurrent colorectal cancer is the topoisomerase I inhibitor irinotecan. Combination of chemotherapy drugs is a common practice in the treatment of cancer. This study investigates the synergistic anti-proliferative effects of irinotecan with cucurbitacin I. The combination of antiproliferative agents can potentiate the therapeutic effects, reduce the dose, and consequently, the toxicity, and minimize or delay cases of drug resistance. Cucurbitacin I is a selective Janus kinase (JAK2)/Signal Transducers and Activators of Transcription (STAT3) signaling pathway inhibitor. Activation of JAK2/STAT3 plays a crucial role in cell survival and proliferation. Thus, the identification of a compound that blocks this pathway would contribute significantly to growth inhibition and apoptosis of tumor cells. The aim of the present study was investigate the effects of cucurbitacin I and combination with irinotecan which have apoptotic anti-migratory, anti-clonogenic and antiproliferative effects on SW620 and LS174T colon cancer cell lines. In addition to this, determination of the exact molecular effects of cucurbitacins would allow us to identify new molecular targets for the treatment of the colon cancer.