THE ETHYL ACETATE FRACTION OF Gynura procumbens SENSITIZES WiDr COLON CANCER CELL LINE AGAINST 5-FLUOROURACIL BUT SHOWS ANTAGONISM WITH CISPLATIN

Nunuk Aries Nurulita, Edy Meiyanto, Sugiyanto Sugiyanto, Eishou Matsuda, Masashi Kawaichi

Abstract


Our recent study has evaluated fraction of ethyl acetate of Gynura procumbens (FEG) as co-chemotherapeutic agent in combination with 5-fluorouracil (5-FU) and cisplatin (CISP) against colon cancer cell line, WiDr cells. This study aims to assess whether FEG show synergism with 5-FU and CISP and to evaluate its regulation on proliferation, cell cycle, and apoptosis on WiDr colon cancer cells.

(3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was performed to determine the growth inhibitory effect of both single (FEG, 5-FU, or CISP) and combination treatments. FEG (25-500 μg/mL),  5-FU (25-1000 μM)  and CISP (5-100 μM) inhibited cells growth in a dose dependent manner and exhibited IC50 value of 125  μg/mL, 848 mM and 43 mM, respectively. FEG sensitizes WiDr cells that was treated by 5-FU, boosting its therapeutic potential. Conversely when FEG was combined with CISP, it caused antagonism.  The antiproliferative effect of single and combination treatment was determined by studying the cell proliferation kinetics under MTT assay. Flowcytometry and (4’,6-diamidino-2-phenylindole) DAPI staining was used to disclose the mechanism of cell cycle arrest and apoptosis. FEG inhibited cell proliferation, induced G1 and S phase arrest and apoptosis. The inhibitory effect was enhanced when FEG was combined with 5-FU, differing from CISP.

According to the datas obtained, FEG appeared to possess sensitizing properties, and caused cell cycle arrest and apoptosis on WiDr cells. FEG demonstrated a possibility of additive to synergism properties when combined with 5-FU but not with CISP.

 

Keywords: Gynura procumbens; WiDr; G1 and S phase arrest; apoptosis.


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DOI: http://dx.doi.org/10.5138/ijpm.v3i3.363

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