Anti-Cancer Properties of Coix Seed Oil against HT-29 Colon Cells through Regulation of the PI3K/AKT Signaling Pathway

This study aims to observe the effects of coix seed oil (CSO) on HT-29 cells and investigate its possible regulation mechanism of the PI3K/Akt signaling pathway. Fatty acid analysis showed that coix seed oil mainly contains oleic acid (50.54%), linoleic acid (33.76%), palmitic acid (11.74%), and stearic acid (2.45%). Fourier transform infrared results found that the fatty acid functional groups present in the oil matched well with the vegetable oil band. The results from CCK-8 assays showed that CSO dose-dependently and time-dependently inhibited the viability of HT-29 cells in vitro. CSO inhibited cell viability, with IC50 values of 5.30 mg/mL for HT-29 obtained after 24 h treatment. Morphological changes were observed by apoptotic body/cell nucleus DNA (Hoechst 33258) staining using inverted and fluorescence microscopy. Moreover, flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. It showed that CSO induced cell apoptosis and cycle arrest in the G2 phase. Quantitative real-time PCR and Western blotting revealed that CSO induced cell apoptosis by downregulating the PI3K/AKT signaling pathway. Additionally, CSO can cause apoptosis in cancer cells by activating caspase-3, up-regulating Bax, and down-regulating Bcl-2. In conclusion, the results revealed that CSO induced G2 arrest and apoptosis of HT-29 cells by regulating the PI3K/AKT signaling pathway.

[1]  Liang Li,et al.  The relationship between charge intensity and bioactivities/processing characteristics of exopolysaccharides from lactic acid bacteria , 2021, LWT.

[2]  F. Deng,et al.  Characterization of extractable components of fresh and fermented Huarong large-leaf mustard and their inhibitory effects on human colon cancer cells , 2021 .

[3]  S. Ralph,et al.  Tea tree oil extract causes mitochondrial superoxide production and apoptosis as an anticancer agent, promoting tumor infiltrating neutrophils cytotoxic for breast cancer to induce tumor regression. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[4]  S. Jasim,et al.  Synergistic anticancer effects of phycocyanin and Citrullus colocynthis extract against WiDr, HCT-15 and HCT-116 colon cancer cell lines , 2021 .

[5]  N. Jaradat,et al.  Nepeta curviflora essential oil: Phytochemical composition, antioxidant, anti-proliferative and anti-migratory efficacy against cervical cancer cells, and α-glucosidase, α-amylase and porcine pancreatic lipase inhibitory activities , 2020 .

[6]  Xin-huai Zhao,et al.  Pretreatment of IEC-6 cells with quercetin and myricetin resists the indomethacin-induced barrier dysfunction via attenuating the calcium-mediated JNK/Src activation. , 2020, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[7]  Wei Zhao,et al.  Optimization of adlay (Coix lacryma-jobi) bran oil extraction: Variability in fatty acids profile and fatty acid synthase inhibitory activities , 2020 .

[8]  Constain H. Salamanca,et al.  Production, physicochemical characterization, and anticancer activity of methotrexate-loaded phytic acid-chitosan nanoparticles on HT-29 human colon adenocarcinoma cells. , 2020, Carbohydrate polymers.

[9]  Feng-ze Wang,et al.  CCT128930 induces G1-phase arrest and apoptosis and synergistically enhances the anticancer efficiency of VS5584 in human osteosarcoma cells. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  Xingrong Ju,et al.  Insoluble-bound polyphenols of adlay seed ameliorate H2O2-induced oxidative stress in HepG2 cells via Nrf2 signalling. , 2020, Food chemistry.

[11]  Jike Lu,et al.  Comparative study on the bioactive components and in vitro biological activities of three green seedlings. , 2020, Food chemistry.

[12]  Hui Fu,et al.  Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway , 2020, Neurochemical Research.

[13]  N. Bie,et al.  A polysaccharide from Grifola frondosa fruit body induces HT-29 cells apoptosis by PI3K/AKT-MAPKs and NF-κB-pathway. , 2020, International journal of biological macromolecules.

[14]  S. Mertens-Talcott,et al.  Dark sweet cherry (Prunus avium) phenolics enriched in anthocyanins exhibit enhanced activity against the most aggressive breast cancer subtypes without toxicity to normal breast cells , 2020 .

[15]  G. Hoxhaj,et al.  The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism , 2019, Nature Reviews Cancer.

[16]  Ahmedin Jemal,et al.  Cancer treatment and survivorship statistics, 2019 , 2019, CA: a cancer journal for clinicians.

[17]  E. Giovannucci,et al.  Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies , 2019, Nature Reviews Gastroenterology & Hepatology.

[18]  Roberto Parra-Saldivar,et al.  Sustainable production of natural phenolics for functional food applications , 2019, Journal of Functional Foods.

[19]  A. Ansari,et al.  Preparation, characterizations and in vitro cytotoxic activity of nickel oxide nanoparticles on HT-29 and SW620 colon cancer cell lines. , 2019, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[20]  L. Dini,et al.  Autophagy in development and regeneration: role in tissue remodelling and cell survival , 2019, The European Zoological Journal.

[21]  Elham Ghadami,et al.  PI3k/AKT signaling pathway: Erythropoiesis and beyond , 2018, Journal of cellular physiology.

[22]  J. Sotelo,et al.  Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma , 2018, International journal of molecular sciences.

[23]  Eun Hee Kim,et al.  Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway , 2018, Nutrients.

[24]  Chunze Zhang,et al.  Kanglaite sensitizes colorectal cancer cells to Taxol via NF-κΒ inhibition and connexin 43 upregulation , 2017, Scientific Reports.

[25]  Zheling Zeng,et al.  Enzymatic production of trans-free shortening from coix seed oil, fully hydrogenated palm oil and Cinnamomum camphora seed oil , 2018 .

[26]  Chendong Yang,et al.  Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway , 2018, OncoTargets and therapy.

[27]  S. Jeong,et al.  Coix lacryma-jobi var. ma-yuen Stapf sprout extract has anti-metastatic activity in colon cancer cells in vitro , 2017, BMC Complementary and Alternative Medicine.

[28]  B. Adhikari,et al.  Physicochemical and thermal characteristics of Australian chia seed oil. , 2017, Food chemistry.

[29]  Shufang Zheng,et al.  Selenium protects against cadmium-induced kidney apoptosis in chickens by activating the PI3K/AKT/Bcl-2 signaling pathway , 2017, Environmental Science and Pollution Research.

[30]  Tzong-Ming Shieh,et al.  The licorice dietary component isoliquiritigenin chemosensitizes human uterine sarcoma cells to doxorubicin and inhibits cell growth by inducing apoptosis and autophagy via inhibition of m-TOR signaling , 2017 .

[31]  Changxiao Liu,et al.  Research and Application of Adlay in Medicinal Field , 2017 .

[32]  Ding Qu,et al.  Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy , 2017, International journal of nanomedicine.

[33]  F. Zhu.  Coix: Chemical composition and health effects , 2017 .

[34]  S. Chou,et al.  Cinnamomum cassia essential oil and its major constituent cinnamaldehyde induced cell cycle arrest and apoptosis in human oral squamous cell carcinoma HSC‐3 cells , 2017, Environmental toxicology.

[35]  Yuerong Liang,et al.  Suppressive Effects of Tea Catechins on Breast Cancer , 2016, Nutrients.

[36]  Zhou Cheng,et al.  Assessment of the Genetic Diversity of Different Job's Tears (Coix lacryma-jobi L.) Accessions and the Active Composition and Anticancer Effect of Its Seed Oil , 2016, PloS one.

[37]  Xi Peng,et al.  Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken’s Tubular Apoptosis Induced by Nickel Chloride (NiCl2) , 2015, International journal of molecular sciences.

[38]  Xuemin Wang,et al.  EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer , 2015, PloS one.

[39]  T. Al-Hattab,et al.  EXTRACTION OF DATE PALM SEED OIL (PHOENIX DACTYLIFERA) BY SOXHLET APPARATUS , 2015 .

[40]  Jiandu Lei,et al.  Extraction of oil from Jatropha curcas seeds by subcritical fluid extraction. , 2014 .

[41]  Sen Lu,et al.  Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell transplantation‑induced tumor growth. , 2014, Molecular medicine reports.

[42]  H. Choo,et al.  Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance. , 2014, Journal of medicinal chemistry.

[43]  Y. Wan,et al.  Kanglaite injection combined with hepatic arterial intervention for unresectable hepatocellular carcinoma: a meta-analysis. , 2014, Journal of cancer research and therapeutics.

[44]  C. Porta,et al.  Targeting PI3K/Akt/mTOR Signaling in Cancer , 2014, Front. Oncol..

[45]  Ding Qu,et al.  Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation , 2013, International journal of nanomedicine.

[46]  H. Chung,et al.  Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. , 2014, Biochimica et biophysica acta.

[47]  Seung Yuan Lee,et al.  Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[48]  X. Jing,et al.  Antitumor activity of folate-targeted, paclitaxelloaded polymeric micelles on a human esophageal EC9706 cancer cell line , 2012, International journal of nanomedicine.

[49]  Shujing Zhang,et al.  Optimizations and comparison of two supercritical extractions of adlay oil , 2012 .

[50]  H. Xiong,et al.  Carboxymethylchitosan-coated proliposomes containing coix seed oil: Characterisation, stability and in vitro release evaluation , 2011 .

[51]  Soo-Jin Jeong,et al.  Are there new therapeutic options for treating lung cancer based on herbal medicines and their metabolites? , 2011, Journal of ethnopharmacology.

[52]  Y. Kuo,et al.  Antiproliferative lactams and spiroenone from adlay bran in human breast cancer cell lines. , 2011, Journal of agricultural and food chemistry.

[53]  Y. Man,et al.  Determination of extra virgin olive oil in quaternary mixture using FTIR spectroscopy and multivariate calibration , 2011 .

[54]  Xianghui Ma,et al.  Anticancer drug discovery in the future: an evolutionary perspective. , 2009, Drug discovery today.

[55]  Yong Zeng,et al.  Inhibition of Coix seed extract on fatty acid synthase, a novel target for anticancer activity. , 2008, Journal of ethnopharmacology.

[56]  Jie Zhang,et al.  Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. , 2004, World journal of gastroenterology.