Anticancer Potential of Cinnamon Bark Extract (Cinnamomum burmanii) with Cisplatin Combination against P-glycoprotein and Apoptotic Influx Biomarkers

Abstract

Objective: To prove the effect of the combination of cinnamon bark extract with cisplatin in reducing efflux and increasing influx in SKOV3 ovarian cancer cell cultures by measuring the expression of p-glycoprotein, CTR1 and the annexim V.
 Methods: This research is an experimental study using SKOV3 ovarian cancer cells stored in the SCTE IMERI FKUI Laboratory, carried out in the Stem Cells and Tissues Engineering Research Cluster laboratory. The cells were then harvested by adding trypsin-EDTA to the culture as much as 1 mL, and rotated at 2000 rpm for 5 minutes. Then the cells were added with antibodies and dissolved with a stain buffer solution and read on a flow cytometry device. We used ethyl acetate extract from cinnamon bark against the SKOV3 cell line . IC50 of Cinnamon bark extract we got from MTS test. We tested the levels of IC50, 3/4 IC50, 1/2 IC50, and 1/4 IC50 of cinnamon bark extract with a combination of IC50, 3/4 IC50 , 1/2 IC50, and 1/4 IC50 cisplatin against the viability of the SKOV3 cell line with single cisplatin IC50 comparator. We also examined the levels of annexin V as a marker of apoptosis in the SKOV3 cell line to see if the cell cycle arrest induced by cinnamon bark extract could cause apoptosis of the SKOV3 cell line. We assessed the sample distribution using the Shapiro-Wilk test because of the sample size . To assess the comparison of parameters (differences in p Glycoprotein and CTR-1 expression between treatment groups in normally distributed data, the test was used analysis of variance (ANOVA). ANOVA is a comparative test to analyze the difference in the mean (mean) of data from two or more variables in the same population. The Bonferroni test was used to analyze the same or different samples (equal and unequal) in each treatment.
 Results: From this study, it was found that the combination of IC 50 cinnamon bark extract and IC 50 cisplatin was able to lower p-glycoprotein levels higher with a lower mean value than the other treatment groups with p<0.001. In the test group, the lowest p-glycoprotein expression was found in the combination 1 test group, namely the 1 x IC50 combination. The value of p-glycoprotein expression in the combination group 1 was 1.20%. As for CTR 1, the combination of IC 50 cinnamon bark and IC 50 cisplatin, had the highest CTR1 levels among the three other treatment groups, with p > 0.001. In the test group, the highest CTR1 expression was found in the combination 1 test group, namely the 1 x IC50 combination. The value of CTR1 expression in the combination group 1 was 12%.
 Conclusion: The combination of cinnamon bark extract with cisplatin was shown to reduce efflux by decreasing p-glycoprotein expression and increasing influx by increasing CTR1 expression in SKOV3 ovarian cancer cell cultures.