Feruloyl-l-arabinose attenuates migration, invasion and production of reactive oxygen species in H1299 lung cancer cells
Graphical abstract
Introduction
Lung cancer is the leading cause of death in the world. The human non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancer cases. More than one of three patients with NSCLC is surgically unavailable (Pirker and Minar, 2010). Until now, chemotherapy is still the major approach in clinical NSCLC treatment (Ettinger et al., 2010, O’Rourke et al., 2010, Pirker and Minar, 2010, Wagner and Yang, 2010). Despite the continuing efforts on improving the current therapies and developing new regimens to treat lung cancers, both poor prognosis at the advanced stage of NSCLC and chemotherapeutic resistance contribute to the low survival rate of NSCLC patients (Wagner and Yang, 2010). Nowadays, numerous anticancer agents derived from natural products (Chiu et al., 2011, Liu, 2011, Wang and Yi, 2008) have been shown to exhibit improved chemopreventive effects against lung cancer, and this may shed the light on the efficacy of lung cancer therapy.
Ferulic acid (FA), or 4-hydroxy-3-methoxycinnamic acid (Fig. 1A), is an abundant aromatic natural constituent found in plant cell walls (Buanafina et al., 2010, Srinivasan et al., 2007). FA is known to exert potent effects on scavenging reactive oxygen species (ROS) and inhibiting lipid peroxidation, and thus has been approved as food additive to prevent lipid peroxidation in certain countries (Srinivasan et al., 2007). Recently, water-soluble FA sugar esters from wheat bran had been reported to stimulate the growth of Bifidobacterium bifidum (Yuan et al., 2005a), and effectively protect normal rat erythrocytes against AAPH-induced oxidative damage (Yuan et al., 2005b). In in vitro studies, water-soluble FA sugar esters were found to possess effective antioxidant activity towards low-density lipoproteins oxidation and exhibit better scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals than FA (Ohta et al., 1997). In addition, water-soluble FA sugar esters exhibited protection capacity against oxidative damage due to diabetes (Ou et al., 2007). Additionally, the major site of FA absorption is the colon, free FA and feruloyl-glucuronide could be efficiently transported through an in vitro model for the colonic epithelium consisting of co-cultured Caco-2 and mucus-producing HT29-MTX cells (Poquet et al., 2008). Based on these observations, FA and water soluble FA sugar esters demonstrated potential to be used as food additive for atherosclerosis prevention or other applications involving its antioxidant capacity.
Previous studies have shown that FA exhibited anti-proliferative effects on colon cancer cells (Janicke et al., 2011, Jayaprakasam et al., 2006), increased the radiosensitizing effects on cervical cancer cells (Karthikeyan et al., 2011) and showed the protective effects against chemical-induced DNA damages and/or carcinogenesis in various model systems (Stagos et al., 2005, Tanaka et al., 1993). In another study however, FA was shown to enhance proliferation of MCF7 and BT20 human breast cancer cells (Chang et al., 2006), indicating the possibility that FA might exhibit different biological effects depending upon cancer cell types it interacts with. However, the antioxidant activity of identified FA sugar esters in a cell model has not yet to be reported. Although FA and its various derivatives have been shown to exhibit the antioxidant effects in vitro and in vivo, they seem to possess diverse pharmacological functions, with some of which still remaining unknown. Therefore, the roles of FA derivatives in cancer cells remained to be fully investigated. To date, studies performed to investigate the direct effects of FA and its derivatives on lung cancer cells have been limited.
In the current study, we purified a FA derivative, feruloyl-l-arabinose (FAA) (Fig. 1B) from coba husk of plant Zizania latifolia, and examined its antioxidant ability on the lung cancer H1299 cell line as many cancers are known to possess elevated ROS levels that enhance their mobility, invasiveness and metastatic capabilities. H1299 cell is a large cell carcinoma, one subtype of non-small cell lung cancer cells, and has been reported to exhibit a high invasiveness compared to other lung cancer cells (Seo et al., 2009, Shatz et al., 2010). We hypothesized that FAA possesses anti-oxidant properties, causing the reduction of intracellular ROS that leads to decreased proliferation, altered cell cycle and reduced mobility in H1299 lung cancer cells. In addition, other effects of FAA, such as the scavenging ability of endogenous ROS, and influence on cellular invasion and proliferatory capacities, on H1299 cells were also examined.
Section snippets
Preparation of FAA
Zizania latifolia coba husk was collected from local farm in Pu-Li, Taiwan. After washed and oven-dried at 60 °C for overnight, samples were milled and passed through a 0.5 mm sieve. Samples were defatted immediately using n-hexane with the Soxhlet apparatus. The dry defatted sample was then used for insoluble dietary fiber (IDF) preparation according to a previously published protocol (Bunzel et al., 2001). The mixtures of phenolic acid sugar esters were prepared from IDF of coba husk by
Radical-scavenging activity of FAA
To evaluate the radical scavenging activity of FAA, the DPPH assay was performed. The antioxidant activity of FAA was measured by assessing the capacity of FAA to scavenge DPPH. The absorbance in solution decreases upon accepting hydrogen atoms from an antioxidant. As shown in Fig. 2B and Supplementary Fig. 2, all concentrations (0.01, 0.03, 0.06, 0.15, 0.3 and 0.6 mM) of FA and FAA tested exhibited significant radical-scavenging activity as compared with the blank control. In addition, higher
Discussion
In our current study, we investigated the ability of FAA, an active FA derivative, to affect migration of lung cancer H1299 cells. Many chemopreventive and anti-cancer agents suffer from poor water-solubility, and therefore their further development in clinical therapeutics is limited. Similarly, the poor water solubility of FA (Maegawa et al., 2007), like other polyphenolic compounds, leads to its reduced bioavailability and may pose practical difficulties in its potential pharmacological
Conflict of Interest
The authors declare that there is no conflict of interest.
Acknowledgements
This work was supported by the grants from ChiMei-KMU Joint Research Project (101-CM-KMU-11), Kaohsiung Medical University, Taiwan (M098007), Kaohsiung Medical University Research Foundation (KMUER-004), NSYSU-KMU Joint Research Project (NSYSUKMU 101-01, 101-14 and 102-28) and the National Science Council, Taiwan (NSC101-2313-B-037-001, NSC101-2622-B-037-002-CC3, NSC101-2320-B-037-046-MY3 and NSC101-2313-B-037-002).
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Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives
2021, Life SciencesCitation Excerpt :Lei et al. designed and synthesized a series of FA-carbazole hybrid compounds, especially compound 5 k (Fig. 7L), which not only showed similar antioxidant activity to FA, but also had better neuroprotective effect than the mixture of FA and carbazole monomer [142]. Feruloyl-L-arabinose (FAA) (Fig. 7M), a derivative of FA isolated from coba husk, has strong antioxidant capacity and can inhibit the migration and invasion of human lung cancer cells (H1299) in a dose-dependent manner [143]. Butyl ferulate (FAC4) (Fig. 7N), one of the derivatives of FA, has a stronger ability to scavenge free radicals induced by extracellular a β aggregates than FA, and can prevent rat adrenal medullary chromaffin tumor cells (PC12) from ROS mediated oxidative stress and apoptosis [144].
Ferulic acid as anticarcinogenic agent against 1,2-dimethylhydrazine induced colon cancer in rats
2021, Journal of King Saud University - ScienceCitation Excerpt :FA also had a significant influence on the proteins of the apoptotic cascade, cyclooxygenase and caspases, decreased cell growth and moderately suppressed colon tumor cells (Palani Swamy and Govindaswamy, 2015). In different cancer cell lines, FA affects cell invasion, migration, and colony formation and could prevent metastasis (Fang et al., 2013). Collectively, we could be concluded that ferulic acid may have a promising therapeutic role against colon cancer induced by 1,2 dimthylhydrazine as indicated by the observed improvement in the histological structure and measured immunohistochemical and gene expression.
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2019, Journal of Functional FoodsCitation Excerpt :A study evidenced that FAA could significantly and concentration-dependently at concentrations of 0.03, 0.06, 0.15, 0.3 and 0.6 mM inhibit the migration and invasion abilities, and induce H1299 cell cycle arrest at G2/M phase. These alterations caused by FAA might be through down-regulating MMP-2 and MMP-9 (Fang et al., 2013). Edible macro-fungi have been used in folk medicine and as a flavor in cuisine, which contain abundant bioactive compounds such as polysaccharides (Guo et al., 2012; Zhang et al., 2016).
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2017, Bioactive Carbohydrates and Dietary FibreFerulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro
2016, GeneCitation Excerpt :FA feeding has been shown to inhibit the growth of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and suppress the progression to malignant neoplasia (Kawabata et al., 2000). In addition, FA derivative feruloyl-L-arabinose (FAA) was also shown to have an effect on H1299 lung cancer cells in attenuating their migration, invasion and reactive oxygen species (ROS) production, suggesting a role for it in chemoprevention just like FA (Fang et al., 2013). On the other hand, despite the chemopreventive functions, FA has also been reported to up-regulate HER2 expression causing proliferation of the human breast cancer cells (Chang et al., 2006).