HCT-116 and HT-29 cells were treated with different concentrations of ferulic acid or 4-vinylguaiacol for 48 h. to 36.8%. Both ferulic acid and 4-vinylguaiacol possessed dose- and time-related anticancer activities on the two cell lines, while 4-vinylguaiacol showed more potent effects than ferulic acid. Interestingly, 4-vinylguaiacol Cimaterol exhibited significantly higher antiproliferative effects on the HT-29 cell line than that on HCT-116. The IC50 of the metabolite Rabbit Polyclonal to ATXN2 4-vinylguaiacol on HT-29 cells was 350 M, 3.7-fold higher than its parent compound. The potential of cancer cell growth inhibition of 4-vinylguaiacol was mediated by cell cycle arrest at the G1 phase and induction of apoptosis. Data from Cimaterol this study indicate that the oral administration of ferulic acid offers a promising approach to increase its anticancer activity through gut microbial conversion to 4-vinylguaiacol, and the biotransformation could also be achieved by selected commercial probiotics. 4-Vinylguaiacol is a potential anticancer metabolite from ferulic acid for chemotherapy-resistant colon cancer cells. 1.?Introduction Cancer, which is one of the leading causes of death in the world, is a multi-step process occurring over an extended time frame, thus there are several possible stages at which the process halted, slowed down, or even reversed.1,2 The clinical cancer management involves diverse conventional modalities including surgery, radiation, and chemotherapy.3 A number of exogenous chemical compounds have been tested for possible chemoprevention activity to prevent, inhibit, or reverse the process of carcinogenesis.4,5 These include dietary constituents, micronutrients, trace elements, and some pharmaceuticals.6 In the past 30 years, nearly 80% of approved anticancer drugs were derived from natural compounds.7 Recently, much attention has been focused on identifying phytochemicals, particularly those included in our diet, which possess the ability to interfere with carcinogenic and mutagenic processes.1 Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies in the world, making up approximately 10% of all cancer cases in both men and women.8 In the United States, it is estimated that there will be 147,950 new cases and 53,200 deaths from CRC in 2020, indicating the inadequacy of currently available treatment modalities.9 However, even though the response rate to current systemic chemotherapies can reach up to 50%, drug resistance Cimaterol reportedly develops in nearly all patients with CRC and limits the therapeutic efficacies of anticancer agents and finally leads to chemotherapeutic failure.10 Controlling the growth of drug-resistant CRC cells becomes a big challenge for the treatment Cimaterol of CRC.8 Therefore, it is necessary and meaningful to find new compounds extracted from botanicals or functional foods in Cimaterol treating CRC, especially the drug-resistant CRC. The two cell lines used in this study varied in p53 expression. HCT-116 is a p53 wild type, whereas HT-29 cells contain a p53 mutation. Cancer cells with p53 mutations are resistant to many chemotherapeutic agents. Thus, the effects of agents on those two types of cell lines reflect the treatment responses of two types of CRC cells, that is, chemo-sensitive and chemo-resistant cells. Ferulic acid (4-hydroxy-3-methoxycinnamic acid), a hydroxycinnamic acid, is abundant in vegetables and grains, such as onions, beans, flaxseeds, corn, wheat, and rice bran.11 Ferulic acid has also been found in many Chinese herbal medicines, such as spp.25 It would be interesting to know whether ferulic acid could be converted to 4-vinylguaiacol by probiotics for potential CRC management. In this project, the biotransformation of ferulic acid to 4-vinylguaiacol by human intestinal microflora and selected probiotics was measured and compared by high-performance liquid chromatography (HPLC), and then the anti-CRC activities of ferulic acid and 4-vinylguaiacol were investigated. In addition to the commonly studied human CRC cell line HCT-116, the drug-resistant CRC cell line HT-29 was used to evaluate whether these two compounds possess anti-CRC effect against the chemo-resistant cell line. The related mechanisms of actions were explored. 2.?Results 2.1. Ferulic Acid Metabolism by Enteric Microbiome and Commercial Probiotics HPLC analysis was used to detect the levels of ferulic acid and its metabolite, 4-vinylguaiacol, after the biotransformation of human enteric microbiome and commercial probiotics. Table 1 shows the regression equation and limits of detection and quantitation (LOD and LOQ, respectively) of ferulic acid and 4-vinylguaiacol, which were considered to be satisfactory for subsequent analysis of all the samples. Table 1 Linear Regression Data, LOD, and LOQ for Ferulic Acid and 4-Vinylguaiacol < 0.05 vs control), while no significant effects were observed on HT-29 cells. At the same concentration (1.0 mM), 4-vinylguaiacol inhibited cancer cell growth by 50.0 3.4% in HCT-116 cells and 85.9 .