Vitexin modifying the expression of APC, p53, KRAS genes with metabolome profile changes in HT-29 colorectal cancer cell line
محورهای موضوعی : مجله گیاهان دارویی
Elham Ghodousi-Dehnavi
1
,
Reza Haji Hosseini
2
,
Mohammad Arjmand
3
,
Sima Nasri
4
,
Zahra Zamani
5
1 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
2 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
3 - Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran;
4 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
5 - Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran;
کلید واژه: Colorectal cancer, Metabolomics, p53, APC, KRAS, Vitexin, 1HNMR,
چکیده مقاله :
Background & Aim: Colorectal canceris a clinically heterogeneous disease resulting from metabolome pattern alterations of many metabolites and their genetic factor interactions in man. Chemotherapy in colorectal cancer is generally followed by multiple side effects, including drug resistance; It is well established that herbal medicines are gaining worldwide interest in treating many cancers. Vitexin is an apigenin flavone glycoside present in hawthorn has exhibited therapeutic properties. This study was performed to assess the antitumor properties of Vitexin on the expression of p53, KRAS, and APC genes and the metabolome profile alterations associated with these genetic modifications.Experimental: Cells were treated with different concentrations of Vitexin, and toxicity and cell growth inhibition were ascertained in vitro using the MTT assay method. Cells were treated with Vitexin, and gene expression was determined. Following metabolome 1HNMR spectroscopy with 1D NOESY protocol and the resulting spectra scrutinized to classify differentiated metabolites and their biochemical pathways. Integrative systems biology analysis software examined the metabolites and the genes, and the main pathways modulated by gene expression were identified.Results: Our finding revealed that a 50% inhibitory concentration for Vitexin was 16.32 μM, while the relative expression of tumor suppressor genes APC and p53 in treated cells enhanced and the expression of the KRAS oncogene gene decreased significantly compared to the control group. The crucial changes in convergent metabolic phenotype with genes were identified in this investigation.Recommended applications/industries: Our findings revealed that Vitexin exhibits antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.
Background & Aim: Colorectal canceris a clinically heterogeneous disease resulting from metabolome pattern alterations of many metabolites and their genetic factor interactions in man. Chemotherapy in colorectal cancer is generally followed by multiple side effects, including drug resistance; It is well established that herbal medicines are gaining worldwide interest in treating many cancers. Vitexin is an apigenin flavone glycoside present in hawthorn has exhibited therapeutic properties. This study was performed to assess the antitumor properties of Vitexin on the expression of p53, KRAS, and APC genes and the metabolome profile alterations associated with these genetic modifications.Experimental: Cells were treated with different concentrations of Vitexin, and toxicity and cell growth inhibition were ascertained in vitro using the MTT assay method. Cells were treated with Vitexin, and gene expression was determined. Following metabolome 1HNMR spectroscopy with 1D NOESY protocol and the resulting spectra scrutinized to classify differentiated metabolites and their biochemical pathways. Integrative systems biology analysis software examined the metabolites and the genes, and the main pathways modulated by gene expression were identified.Results: Our finding revealed that a 50% inhibitory concentration for Vitexin was 16.32 μM, while the relative expression of tumor suppressor genes APC and p53 in treated cells enhanced and the expression of the KRAS oncogene gene decreased significantly compared to the control group. The crucial changes in convergent metabolic phenotype with genes were identified in this investigation.Recommended applications/industries: Our findings revealed that Vitexin exhibits antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.
Aiello, P., Sharghi, M., Mansourkhani, S. M., Ardekan, A. P., Jouybari, L., Daraei, N. and Kooti, W. 2019. Medicinal plants in the prevention and treatment of colon cancer. Oxidative Medicine and Cellular Longevity, 2019 (4): 5614-5664.
Babaei, F., Moafizad, A., Darvishvand, Z., Mirzababaei, M., Hosseinzadeh, H. and Nassiri‐Asl, M. 2020. Review of the effects of vitexin in oxidative stress-related diseases. Food Science and Nutrition, 8(6): 2569-2580.
Bhardwaj, M., Cho, H. J., Paul, S., Jakhar, R., Khan, I., Lee, S. J. and Kang, S. C. 2018. Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells. Oncotarget, 9(3): 3278–3291.
Chen, J., Zhong, J., Liu, Y., Huang, Y., Luo, F., Zhou, Y. and Wang, J. 2018. Purified vitexin compound 1, a new neolignan isolated compound, promotes PUMA‐dependent apoptosis in colorectal cancer. Cancer Medicine, 7(12): 6158-6169.
Choi, J. W., Kim, D. G., Lee, A. E., Kim, H. R., Lee, J. Y., Kwon, N. H. and Kim, S. 2011. Cancer-associated splicing variant of tumor suppressor AIMP2/p38: pathological implication in tumorigenesis. PLoS Genetics, 7(3): e1001351-e1001365.
Choi, Y. K., and Park, K. G. 2018. Targeting glutamine metabolism for cancer treatment. Biomolecules and Therapeutics, 26(1): 19-28.
Dufour, E., Gay, F., Aguera, K., Scoazec, J. Y., Horand, F., Lorenzi, P. L., and Godfrin, Y. 2012. Pancreatic tumor sensitivity to plasma L-asparagine starvation. Pancreas, 41(6): 940-948
Fam, K. T., Collot, M., and Klymchenko, A. S. 2020. Probing biotin receptors in cancer cells with rationally designed fluorogenic squaraine dimers. Chemical Science, 11(31): 8240-8248.
Ganesan, K. and Xu, B. 2017. Molecular targets of vitexin and isovitexin in cancer therapy: a critical review. Annals Of The New York Academy of Sciences, 1401(1): 102-113.
Gao, W., Chen, L., Ma, Z., Du, Z., Zhao, Z., Hu, Z. and Li, Q. 2013. Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology, 145(3): 636-646.
Green, M. R. and Sambrook, J. 2018. Quantification of RNA by real-time reverse transcription-polymerase chain reaction (RT-PCR). Cold Spring Harbor Protocols, 2018(10): 1101-1110.
Greenfield, R. S. and Wellner, D. 1977. Effects of threonine deaminase on growth and viability of mammalian cells in tissue culture and its selective cytotoxicity toward leukemia cells. Cancer Research, 37(8): 2523-2529.
Holzer, K., Drucker, E., Roessler, S., Dauch, D., Heinzmann, F., Waldburger, N. and Singer, S. 2017. Proteomic analysis reveals GMP synthetase as p53 repression target in liver cancer. The American Journal of Pathology, 187(2): 228-235.
Huang, J., Long, Z., Lin, W., Liao, X., Xie, Y., Liu, L., and Ma, W. 2018. Integrative omics analysis of p53‐dependent regulation of metabolism. FEBS Letters, 592(3): 380-393.
Kim, H. R., Roe, J. S., Lee, J. E., Hwang, I. Y., Cho, E. J. and Youn, H. D. 2012. A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH. Biochemical And Biophysical Research Communications, 418(4): 682-688.
Kodama, M., Oshikawa, K., Shimizu, H., Yoshioka, S., Takahashi, M., Izumi, Y. and Nakayama, K. I. 2020. A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer. Nature Communications, 11(1): 1-16.
Kumar, P., Nagarajan, A., & Uchil, P. D. 2018. Analysis of cell viability by the lactate dehydrogenase assay. Cold Spring Harbor Protocols, 2018(6): 1101-1103.
Kurmi, K., and Haigis, M. C. 2020. Nitrogen metabolism in cancer and immunity. Trends in Cell Biology, 30(5): 408-424.
Li, H., Tian, Y., Li, X., Wang, B., Zhai, D., Bai, Y. and Chao, X. 2019. Knockdown of IARS2 inhibited proliferation of acute myeloid leukemia cells by regulating p53/p21/PCNA/eIF4E pathway. Oncology Research, 27(6):673-680.
Li, T. and Deng, P. 2017. Nuclear magnetic resonance technique in tumor metabolism. Genes Diseases. 4(1): 28-36.
Liang, Y., Liu, J. and Feng, Z. 2013. The regulation of cellular metabolism by tumor suppressor p53. Cell and Bioscience, 3(1): 1-10.
Liu X, Jiang Q, Liu H, Luo S. 2019. Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells. Biological Research. 52(1):1-7.
Liu, N., Wang, K. S., Qi, M., Zhou, Y. J., Zeng, G. Y., Tao, J. and Peng, C. 2018. Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels. Journal of Experimental and Clinical Cancer Research, 37(1): 1-16.
Long, Z., Zhou, J., Xie, K., Wu, Z., Yin, H., Daria, V. and Cui, Y. 2020. Metabolomic markers of colorectal tumor with different clinicopathological features. Frontiers In Oncology, 10: 981-993.
Ng, C., Li, H., Wu, W.K.K., Wong, SH, Yu, J. 2019. Genomics and metagenomics of colorectal cancer. Journal of Gastrointestinal Oncology, 10(6): 1164.
Nie, C., He, T., Zhang, W., Zhang, G. and Ma, X. 2018. Branched chain amino acids: beyond nutrition metabolism. International journal of molecular sciences, 19(4), 954-962.
Ogunwobi, O.O., Mahmood, F., Akingboye, A. 2020. Biomarkers in colorectal cancer: current research and future prospects. International Journal of Molecular Sciences, 21(15): 5311-5334.
Pakiet, A., Kobiela, J., Stepnowski, P., Sledzinski, T. and Mika, A. 2019. Changes in lipids composition and metabolism in colorectal cancer: a review. Lipids In Health and Disease, 18(1): 1-21.
Peng, Y., Renyou, G., Huabin, L., Mingxuan, Yang., David, J. M., Ruichang, G. and Quancai, S. 2021. Absorption, metabolism, and bioactivity of vitexin: recent advances in understanding the efficacy of an important nutraceutical. Critical Reviews in Food Science and Nutrition, 61(6): 1049-1064.
Ping, Y., Xu, C., Xu, L., Liao, G., Zhou, Y., Deng, C. and Li, X. 2020. Prioritizing Gene Cascading Paths to Model Colorectal Cancer Through Engineered Organoids. Frontiers in Bioengineering and Biotechnology, 8:12-38.
Rodriguez-Melendez, R. and Zempleni, J. 2003. Regulation of gene expression by biotin☆. The Journal of Nutritional Biochemistry, 14(12): 680-690.
Saborano, R., Eraslan, Z., Roberts, J., Khanim, F. L., Lalor, P. F., Reed, M. A. and Günther, U. L. 2019. A framework for tracer-based metabolism in mammalian cells by NMR. Scientific Reports, 9(1), 1-13.
Schiliro, C. and Firestein, B. L. 2022. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells, 10(5): 1056-1097.
Shoshan, E., Mobley, A. K., Braeuer, R. R., Kamiya, T., Huang, L., Vasquez, M. E. and Bar-Eli, M. 2015. Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis. Nature Cell Biology, 17(3): 311-321.
Soto-Pantoja, D. R., Sipes, J. M., Martin-Manso, G., Westwood, B., Morris, N. L., Ghosh, A. and Roberts, D. D. 2016. Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the ApcMin/+ model of colon cancer. Oncogenesis, 5(5): 230-237.
Toda, K., Kawada, K., Iwamoto, M., Inamoto, S., Sasazuki, T., Shirasawa, S. and Sakai, Y. 2016. Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia, 18(11): 654-665.
Wang, D., Zhao, R., Qu, Y. Y., Mei, X. Y., Zhang, X., Zhou, Q. and Zhao, J. Y. 2018. Colonic lysine homocysteinylation induced by high-fat diet suppresses DNA damage repair. Cell Reports, 25(2): 398-412.
Wang, J., Alexander, P. and McKnight, S. L. 2011. Metabolic specialization of mouse embryonic stem cells. Cold Spring Harbor Laboratory Symposia Quantitative Biology. 76: 183-193.
Wang, J., Liu, L., Qiu, H., Zhang, X., Guo, W., Chen, W. and Deng, W. 2013. Ursolic acid simultaneously targets multiple signaling pathways to suppress proliferation and induce apoptosis in colon cancer cells. PloS One, 8(5):1-13.
Wu, Z., Wei, D., Gao, W., Xu, Y., Hu, Z., Ma, Z. and Li, Q. 2015. TPO-induced metabolic reprogramming drives liver metastasis of colorectal cancer CD110+ tumor-initiating cells. Cell Stem Cell, 17 (1): 47-59.
Yin, J., Ren, W., Huang, X., Deng, J., Li, T. and Yin, Y. 2018. Potential mechanisms connecting purine metabolism and cancer therapy. Frontiers in Immunology. 30. (9):16979-89.
Yoshie, T., Nishiumi, S., Izumi, Y., Sakai, A., Inoue, J., Azuma, T. and Yoshida, M. 2012. Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. Cancer Science, 103(6): 1010-1021.
Yusof, H. M., Ab-Rahim, S., Suddin, L. S., Saman, M. S. A. and Mazlan, M. 2018. Metabolomics profiling on different stages of colorectal cancer: A systematic review. The Malaysian Journal of Medical Sciences: MJMS, 25(5): 16.
Zeitouni, D., Pylayeva-Gupta, Y., Der, C. J.and Bryant, K. L. 2016. KRAS mutant pancreatic cancer: no lone path to an effective treatment. Cancers. 8(4): 45-53.
Zhang, J., Wang, C., Chen, M., Cao, J., Zhong, Y., Chen, L. and Xia, D. 2013. Epigenetic silencing of glutaminase 2 in human liver and colon cancers. BMC Cancer, 13(1): 1-9.
Zheng, Y., Delgoffe, G. M., Meyer, C. F., Chan, W. and Powell, J. D. 2009. Anergic T cells are metabolically anergic. The Journal of Immunology, 183(10): 6095-6101.
Zhou, Z., Sun, B., Nie, A., Yu, D. and Bian, M. 2020. Roles of aminoacyl-tRNA synthetases in cancer. Frontiers in Cell and Developmental Biology, 8.27: 1446-1453.
