Antitumor Activity of Ferulic Acid and Its Colonic Metabolites

doi:10.12141/j.issn.1000-565X.220113

Abstract

Abstract:

Ferulic acid (FA) is a common dietary polyphenol which is widely found in plant tissues. It has various biological activities such as antioxidant, anti-inflammatory, antithrombotic, and hypoglycemic. Due to the biological activities of dietary polyphenols largely depend on their digestion and absorption in vivo, studies on the intestinal metabolites of dietary polyphenols have gradually attracted researchers’ interest in recent years. Ferulic acid cannot be absorbed in the stomach and small intestine, but it can be converted into a series of hydroxyphenylpropionic acid compounds under the action of colonic esterases. This study selected three main colonic metabolites of FA, namely, 3-(3,4-dihydroxyphenyl) propionic acid (3,4diOHPPA), 3-(3-hydroxyphenyl) propionic acid (3OHPPA) and 3-phenylpropionic acid (PPA), to evaluate their antioxidant and antitumor activities. The results show that the antioxidant activity of metabolite 3,4diOHPPA is superior to that of FA and metabolites 3OHPPA and 3PPA. FA and its three metabolites can significantly inhibit the proliferation of HepG2 with EC50 values of 1.82 mmol/L (FA), 0.74 mmol/L (3,4diOHPPA), 7.77 mmol/L (3PPA) and 4.52 mmol/L (3PPA), respectively. Cell-cycle experiments show that FA and its three metabolites can regulate HepG2 cell cycle progression in an orderly manner, blocking the cell cycle in G2 or S phase. FA and its three metabolites can also induce apoptosis of HepG2 in a dose-dependent manner. Among them, FA and 3,4diOHPPA can increase the total apoptosis rate of HepG2 cells to 15.47% and 71.84% (4.23% for the control). After a pretreatment for 24 h, FA exerts its antiproliferative effects by upregulating Bax, p53 genes and downregulating CDK-2, CDK-4 genes; 3,4diOHPPA inhibits the proliferation of HepG2 by upregulating Bax, caspase-3 genes and downregulating CDK-2, CDK-4 genes. All these findings show that the anti-oxidative and anti-HepG2 cell proliferation ability of the metabolite 3,4diOHPPA is superior to that of FA. This research provides theoretical support for the antitumor activity of FA and its colonic metabolites, revealing the health benefits of FA intestinal metabolites.

Key words: ferulic acid, colonic metabolites, antitumor activity, proliferation

CLC Number:

ZHENG Bisheng, YANG Wenhan, XU Qiuxiong, et al. Antitumor Activity of Ferulic Acid and Its Colonic Metabolites[J]. Journal of South China University of Technology(Natural Science Edition), 2022, 50(8): 30-40.

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基因		基因序列（5′-3′）
β-actin	F	GTTGCTATCCAGGCTGTGC
β-actin	R	GCATCCTGTCGGCAATGC
p53	F	CCCCTCCTCAGCATCTTA
p53	R	ACAAACACGCACCTCAAA
Bax	F	TTTGCTTCAGGGTTTCATCC
Bax	R	CAGTTGAAGTTGCCGTCAGA
Caspase-3	F	GTGCTATTGTGAGGCGGTTG
Caspase-3	R	TCCAGAGTCCATTGATTCGCTT
CDK-2	F	CGCTTCATGGAGAACTTC
CDK-2	R	ATGGCAGAAAGCTAGGCC
CDK-4	F	CTGGACACTGAGAGGGCAAT
CDK-4	R	TGGGAAGGAGAAGGAGAAGC

样品	EC₅₀	PSC^1）
FA	51.90±7.52	0.58±0.09
3，4diOHPPA	31.94±2.34	0.94±0.07
3OHPPA	61.30±1.05	0.65±0.01
3PPA	25.98±3.59	1.55±0.20

样品	CAA^1）		细胞吸收率/%
样品	无PBS清洗	PBS清洗	细胞吸收率/%
FA	5.01±0.57	1.72±0.05	13.88±0.01
3，4diOHPPA	14.95±0.29	5.89±0.38	39.42±0.03
3OHPPA	0.77±0.06	0.70±0.02	91.22±4.73
3PPA	0.38±0.02	0.30±0.00	79.89±3.60

样品	EC₅₀/（mmol·L^-1）	CC₅₀/（mmol·L^-1）	SI
FA	1.82±0.07	4.50±0.02	2.47
3，4diOHPPA	0.74±0.06	3.32±0.01	4.49
3OHPPA	7.77±0.05	20.60±0.46	2.65
3PPA	4.52±0.05	14.08±0.26	3.12

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