Abstract
Purpose: To evaluate the synergistic cytotoxicity of sodium dichloroacetate (DCA) in combination with cisplatin (CIS) against human cervical cancer cell lines.
 Methods: Cervical cancer SiHa and HeLa cells and normal cells (Hek-293, Vero, peripheral blood mononuclear and human erythrocytes) were treated in vitro with DCA and CIS individually or their combination. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method while hemolytic activity was evaluated from the released hemoglobin. Halfmaximal inhibitory concentration (IC50) of DCA or CIS was obtained.
 Results: The combination of DCA + CIS decreased the cell viability of SiHa, Hek-293, Vero, and PBMC cells, but not of Hela cells (p < 0.05). Furthermore, the individual treatments alone or in combination did not cause significant hemolysis (p < 0.05).
 Conclusion: The combination of DCA + CIS increases the damage caused by CIS alone on SiHa cells. It also decreases the cell viability of Hek-293 and Vero without affecting peripheral blood mononuclear and human erythrocyte integrity. The results suggest that the combination of DCA and CIS can induce synergistic antitumor effect in different types of cancer cell lines. However, further studies are required to determine the biological effects of the combination of DCA and CIS in vivo.
 Keywords: Cervical cancer, Sodium dichloroacetate, Cisplatin, Viability, Hemolysis
Highlights
Cervical cancer is a disease of high prevalence, incidence, and mortality
The results demonstrated that DCA significantly decreased the viability of SiHa cells in a concentration-dependent manner, finding a 98 % decrease in viability in concentrations of 2.56 x 105 to 3.66 x 105 μM
In the SiHa cells, cisplatin induced a reduction on viability of 62.32 % and 99 % in HeLa cells (Figure 1 C)
Summary
Cervical cancer is a disease of high prevalence, incidence, and mortality. According to the World Health Organization (WHO) in 2018, this disease caused 570 000 new cases of which approximately 270,000 women died, representing 7.5 % of female mortality due to malignant tumors. Some of these include Bithionol that potentiated the cytotoxicity induced by cisplatin on human ovarian cancer cell lines (A2780 and IGROV), caffeic acid in combination with CIS significantly inhibited cell proliferation of HeLa and CaSki cervical cancer cells These combinations have not been effective in the clinical phase [6]. We investigated the cytotoxic effect of DCA in combination with CIS in human cervical cancer cells as well as toxicity in peripheral blood mononuclear cells and erythrocytes. SiHa, HeLa, Hek293 and Vero cells treated with DCA, CIS alone or in combination were observed in the culture plates using an inverted optical microscope (Leica DMIL, USA) and photographs were taken with an attached camera. Where As, An and Ap are the absorbance of sample, negative control and positive control, respectively
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