Abstract
Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.
Highlights
A cycle-specific antimetabolite, 5-fluorouracil (5-FU) is an antineoplastic chemotherapeutic agent that is widely used in the treatment of colorectal cancer (CRC)
We describe 5-FU in combination with another sulforaphane analog, 2-oxohexyl isothiocyanate (2-oxohexyl ITC), which has a different structural modification and demonstrated relevant anticancer properties in previous studies
Cell growth was determined after combination treatment and individual treatment using an MTT assay in prostate cancer cell lines LNCaP and PC-3 and in colon cancer cell lines HT-29 and Caco-2 (Figure 2)
Summary
A cycle-specific antimetabolite, 5-fluorouracil (5-FU) is an antineoplastic chemotherapeutic agent that is widely used in the treatment of colorectal cancer (CRC) It was introduced into clinical use over 50 years ago; despite progress in novel cancer therapies, it remains the mainstay of systemic colorectal cancer treatment and the main constituent of chemotherapy combination regimens [1]. Drug resistance as well as toxic side effects (e.g., increased risks of infection, anemia, and diarrhea) are the main obstacles to the successful treatment of colon cancer [1,2]. For this reason, several 5-FUbased combination regimens have been proposed to increase antitumor activity, reduce the side effects, and overcome clinical resistance. 5-FU is frequently combined with oxaliplatin and irinotecan, and such combined therapies (with LV) have become established as regimens for the treatment of CRC, resulting in an improved survival rate of approximately two years [4,5]
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