Serdar KARAKURT, Gulsum ABUSOGLU, Zekiye Ceren ARİTULUK

Comparison of anticarcinogenic properties of Viburnum opulus and its active compound p-coumaric acid on human colorectal carcinoma

Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatment of colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p-coumaric acid (p-CA), on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO on controlled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p-CAis the main compound of EVO. EVO and p-CA inhibit the proliferation of human colon cancer cells DLD-1 and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells. mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p-CA. EVO and p-CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p-CA.

Keywords:

Colorectal carcinoma, Viburnum opulus, p-coumaric acid, TP53 BRAF, apoptosis, cell cycle,

PDF

___

Al-Hazzani AA, 2011, FOOD CHEM TOXICOL, V49, P3281, DOI 10.1016/j.fct.2011.09.023
Aladhraei M, 2019, J GASTROINTEST ONCOL, V10, P437, DOI 10.21037/jgo.2019.01.17
Alshatwi AA, 2010, J EXP CLIN CANC RES, V29, DOI 10.1186/1756-9966-29-167
Apak R, 2004, J AGR FOOD CHEM, V52, P7970, DOI 10.1021/jf048741x
Beijers AJM, 2012, NETH J MED, V70, P18 .
BRAND-WILLIAMS W, 1995, FOOD SCI TECHNOL-LEB, V28, P25
Cam M, 2007, ACTA ALIMENT HUNG, V36, P381, DOI 10.1556/AAlim.36.2007.3.10
Cao DZ, 2017, ONCOL LETT, V13, P3538, DOI 10.3892/ol.2017.5929
Caronia LM, 2011, CLIN CANCER RES, V17, P7511, DOI 10.1158/1078-0432.CCR-11-1155
Celik G, 2016, EUR J DRUG METAB PH, V41, P109, DOI 10.1007/s13318-014-0238-1
Ceylan D, 2018, J CANCER RES THER, V14, P314, DOI 10.4103/0973-1482.181173
Chang CC, 2002, J FOOD DRUG ANAL, V10, P178
Chang YS, 2019, CANCER MED-US, V8, P3738, DOI 10.1002/cam4.2282
Chen XG, 2017, CELL J, V18, P493 .
Cunningham D, 2010, LANCET, V375, P1030, DOI 10.1016/S0140-6736(10)60353-4
Dawood M, 2019, FRONT PHARMACOL, V10, DOI 10.3389/fphar.2019.00542
de Kok TM, 2008, EUR J NUTR, V47, P51, DOI 10.1007/s00394-008-2006-y
Evdokiou A, 2002, INT J CANCER, V99, P491, DOI 10.1002/ijc.10376
Ewing I, 2007, CLIN ENDOCRINOL, V66, P348, DOI 10.1111/j.1365-2265.2006.02735.x
Ezov LA, 2000, VSE JAGODACH NOVAJA, P311
Globocan, 2014, EST CANC INC MORT PR .
Jaganathan SK, 2013, WORLD J GASTROENTERO, V19, P7726, DOI 10.3748/wjg.v19.i43.7726
Janicke B, 2011, NUTR CANCER, V63, P611, DOI 10.1080/01635581.2011.538486
Jiang B, 2018, J BIOL CHEM, V293, P9747, DOI 10.1074/jbc.RA117.001385
Johnson CM, 2013, CANCER CAUSE CONTROL, V24, P1207, DOI 10.1007/s10552-013-0201-5
Karacelik AA, 2015, FOOD CHEM, V175, P106, DOI 10.1016/j.foodchem.2014.11.085
Karakurt S, 2016, ANTI-CANCER AGENT ME, V16, P781, DOI 10.2174/1871520616666151111115809
Karakurt S, 2016, NUTR CANCER, V68, P173, DOI 10.1080/01635581.2016.1115092
Kizilay F, 2019, TURK J UROL, V45, P63, DOI 10.5152/tud.2019.23463
Kwon JH, 2018, J PATHOL TRANSL MED, V52, P157, DOI 10.4132/jptm.2018.03.28
Massague J, 2008, CELL, V134, P215, DOI 10.1016/j.cell.2008.07.001
Moldovan B, 2017, MAT SCI ENG C-MATER, V79, P720, DOI 10.1016/j.msec.2017.05.122
Moldovan B, 2012, REV CHIM-BUCHAREST, V63, P463
Namani A., 2017, CURR PHARM REP, V3, P221, DOI DOI 10.1007/s40495-017-0101-6
Russell W, 2011, P NUTR SOC, V70, P389, DOI 10.1017/S0029665111000152
Sharma SH, 2018, CHEM-BIOL INTERACT, V291, P16, DOI 10.1016/j.cbi.2018.06.001
Sheng SH, 2019, BIOSCIENCE REP, V39, DOI 10.1042/BSR20181895
SLINKARD K, 1977, AM J ENOL VITICULT, V28, P49
Ulger H, 2013, TOXICOL IND HEALTH, V29, P824, DOI 10.1177/0748233712445049
Velioglu YS, 2006, INT J FOOD SCI TECH, V41, P1011, DOI [10.1111/j.1365-2621.2006.01142.x, 10.1111/j.1365-2621.2005.01142.x]
Wang D, 2019, MED SCI MONITOR, V25, P3796, DOI 10.12659/MSM.913911
Wu MS, 2019, J CELL MOL MED, V23, P5692, DOI 10.1111/jcmm.14482
Yan W, 2018, CANCER MANAG RES, V10, P5479, DOI 10.2147/CMAR.S178261
Ying TH, 2013, ANTICANCER RES, V33, P4411
Yotova IY, 2011, HUM REPROD, V26, P885, DOI 10.1093/humrep/der010
Zhang L, 2017, JNCI-J NATL CANCER I, V109, DOI 10.1093/jnci/djw332
Zhang YC, 2015, ACSR ADV COMPUT, V18, P686
Zhao M, 2018, INT J BIOL SCI, V14, P111, DOI 10.7150/ijbs.23230