Synergistic Antitumor Effect of Dichloroacetate in Combination with 5‐Fluorouracil in Colorectal Cancer

Abstract

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro.

Colon cancer cells treated with 5-fluorouracil exhibit changes in polylactosamine-type N-glycans

“…In the present study, the IC 50 -value of 5-FU on colon cancer cells over a 48-h treatment period was determined in vitro using the MTT assay. The obtained IC 50 -value in regard to a 48-h exposure of SW620 to 13 µg/ml 5-FU was comparable with that previously observed (14). Since the PPC of 5-FU in colon cancer patients is ~10 µg/ml, the data of the present study are clinically relevant.…”

Gelam Honey and Ginger Potentiate the Anti Cancer Effect of 5-FU against HCT 116 Colorectal Cancer Cells

“…However, there was no synergism between ginger extract and Gelam honey in inducing apoptosis of HCT 116 cells (Figure 3). 5-FU, a chemotherapy drug used in the treatment of many cancer types, was shown in earlier studies to interact synergistically with either triptolide or dichloroacetate in killing HT29 cells (Tang et al, 2007;Tong et al, 2011). Combination treatment of 5-FU with dichloroacetate enhanced the 5-FU cytotoxicity and hence reduced the effective drug dose from 798.4µM to 80.0µM (Tang et al, 2007).…”

The Biological Activity of Sodium Dichloroacetate and Its Effectiveness During the Experimental Clinical Studies

“…Было установлено дозозависимое ингиби-рование роста, а также блокирование клеточно-го цикла и апоптоз в случае со злокачественны-ми клетками, в то время как на здоровые клетки никакого влияния не отмечалось [29]. Во втором исследовании клетки колоректального рака об-рабатывались НДХА вместе с 5-фторурацилом -химиотерапевтическим препаратом первой линии при данных опухолях [54]. Результаты продемон-стрировали синергическое антипролиферативное действие, блокирование клеточного цикла и апоп-тоз злокачественных клеток.…”

“…Результаты продемон-стрировали синергическое антипролиферативное действие, блокирование клеточного цикла и апоп-тоз злокачественных клеток. На основании этих результатов авторы предполагают, что такая ком-бинация может повысить эффективность терапии за счет потенцирования действия химиотерапев-тических препаратов [54]. Третье исследование посвящено изучению влияния гипоксии на апоптоз клеток колоректального рака in vitro и in vivo [40].…”