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Research Articles

Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer

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Pages 14135-14151 | Received 19 Dec 2022, Accepted 02 Feb 2023, Published online: 21 Mar 2023

References

  • Yang, H. J., Xue, J. M., Li, J., Wan, L. H., & Zhu, Y. X. (2020). Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis. Molecular Genetics & Genomic Medicine, 8(6), e1200.
  • Balkwill, F. (2004). The significance of cancer cell expression of the chemokine receptor CXCR4. Seminars in Cancer Biology, 14(3), 171–179.
  • Hung, J. Y., Hsu, Y. L., Li, C. T., Ko, Y. C., Ni, W. C., Huang, M. S., & Kuo, P. L. (2009). 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells. Journal of Agricultural and Food Chemistry, 57(20), 9809–9816.
  • Adnan, M., Siddiqui, A. J., Hamadou, W. S., Snoussi, M., Badraoui, R., Ashraf, S. A., … Patel, M. (2021). Deciphering the molecular mechanism responsible for efficiently inhibiting metastasis of human non-small cell lung and colorectal cancer cells targeting the matrix metalloproteinases by Selaginella repanda. Plants, 10(5), 979.
  • Al Moustafa, A. E., Yasmeen, A., & Achkhar, A. (2011). Src inhibitors are promising therapy molecules for human cervical carcinomas. Medical Hypotheses, 77(5), 812–814.
  • Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Finding the cancer-critical genes. In Molecular biology of the cell (4th ed.). Garland Science.
  • Ali, B. H., Blunden, G., Tanira, M. O., & Nemmar, A. (2008). Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food and Chemical Toxicology, 46(2), 409–420.
  • Ali, S., & Coombes, R. C. (2002). Endocrine-responsive breast cancer and strategies for combating resistance. Nature Reviews Cancer, 2(2), 101–112.
  • Alquran, H., Alsalatie, M., Mustafa, W. A., Al Abdi, R., & Ismail, A. R. (2022). Cervical net: A novel cervical cancer classification using feature fusion. Bioengineering, 9, 578.
  • An, T., Gong, Y., Li, X., Kong, L., Ma, P., Gong, L., Zhu, H., Yu, C., Liu, J., Zhou, H., Mao, B., & Li, Y. (2017). USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth. Biochemical Pharmacology, 131, 29–39. https://doi.org/10.1016/j.bcp.2017.02.011
  • Awadelkareem, A. M., Al-Shammari, E., Elkhalifa, A. O., Adnan, M., Siddiqui, A. J., Mahmood, D., … Ashraf, S. A. (2022). Anti-adhesion and antibiofilm activity of Eruca sativa miller extract targeting cell adhesion proteins of food-borne bacteria as a potential mechanism: Combined in vitro-in silico approach. Plants, 11(5), 610.
  • Azmi, A. S. (2012). Network pharmacology for cancer drug discovery: Are we there yet? Future Medicinal Chemistry, 4(8), 939–941.
  • Baselga, J. (2002). Why the epidermal growth factor receptor? The rationale for cancer therapy. The Oncologist, 7(S4), 2–8.
  • Berger, S. I., & Iyengar, R. (2009). Network analyses in systems pharmacology. Bioinformatics, 25(19), 2466–2472.
  • Bertelsen, B. I., Steine, S. J., Sandvei, R., Molven, A., & Laerum, O. D. (2006). Molecular analysis of the PI3K‐AKT pathway in uterine cervical neoplasia: Frequent PIK3CA amplification and AKT phosphorylation. International Journal of Cancer, 118(8), 1877–1883.
  • Bhalla, Y., Gupta, V. K., & Jaitak, V. (2013). Anticancer activity of essential oils: A review. Journal of the Science of Food and Agriculture, 93(15), 3643–3653.
  • Bhatt, M., Patel, M., Adnan, M., & Reddy, M. N. (2021). Anti-metastatic effects of lupeol via the inhibition of MAPK/ERK pathway in lung cancer. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 21(2), 201–206.
  • Bjorge, J. D., Pang, A., & Fujita, D. J. (2000). Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. The Journal of Biological Chemistry, 275(52), 41439–41446.
  • Burotto, M., Chiou, V. L., Lee, J. M., & Kohn, E. C. (2014). The MAPK pathway across different malignancies: a new perspective. Cancer, 120(22), 3446–3456.
  • Chandrashekar, D. S., Bashel, B., Balasubramanya, S. A. H., Creighton, C. J., Ponce-Rodriguez, I., Chakravarthi, B. V., & Varambally, S. (2017). UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 19(8), 649–658.
  • Cohen, P. A., Jhingran, A., Oaknin, A., & Denny, L. (2019). Cervical cancer. The Lancet, 393(10167), 169–182.
  • Córdova-Alarcón, E., Centeno, F., Reyes-Esparza, J., García-Carrancá, A., & Garrido, E. (2005). Effects of HRAS oncogene on cell cycle progression in a cervical cancer-derived cell line. Archives of Medical Research, 36(4), 311–316.
  • Dehm, S. M., & Bonham, K. (2004). SRC gene expression in human cancer: The role of transcriptional activation. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire, 82(2), 263–274.
  • DeVine, T., & Dai, M. S. (2013). Targeting the ubiquitin-mediated proteasome degradation of p53 for cancer therapy. Current Pharmaceutical Design, 19(18), 3248–3262.
  • Du, L., Rao, G., Wang, H., Li, B., Tian, W., Cui, J., He, L., Laffin, B., Tian, X., Hao, C. and Liu, H. (2013). CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal CancerPrPc + metastatic cancer stem cells. Cancer Research, 73(8), 2682–2694.
  • Dugasani, S., Pichika, M. R., Nadarajah, V. D., Balijepalli, M. K., Tandra, S., & Korlakunta, J. N. (2010). Comparative antioxidant and anti-inflammatory effects of [6]-gingerol,[8]-gingerol,[10]-gingerol and [6]-shogaol. Journal of Ethnopharmacology, 127(2), 515–520.
  • Elasbali, A. M., Al-Soud, W. A., Al-Oanzi, Z. H., Qanash, H., Alharbi, B., Binsaleh, N. K., … Adnan, M. (2022). Cytotoxic activity, cell cycle inhibition, and apoptosis-inducing potential of athyrium hohenackerianum (Lady Fern) with its phytochemical profiling. Evidence-Based Complementary and Alternative Medicine, 2022. https://doi.org/10.1155/2022/2055773
  • Elmore, S. (2007). Apoptosis: a review of programmed cell death. Toxicologic Pathology, 35(4), 495–516.
  • Faried, L.S., Faried, A., Kanuma, T., Sano, T., Nakazato, T., Tamura, T., Kuwano, H. and Minegishi, T. (2006). Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy. Oncology Reports, 16(1), 57–63.
  • Formenti, S., Felix, J., Salonga, D., Danenberg, K., Pike, M. C., & Danenberg, P. (2000). Expression of metastases-associated genes in cervical cancers resected in the proliferative and secretory phases of the menstrual cycle. Clinical Cancer Research, 6(12), 4653–4657.
  • Friebel-Klingner, T.M., Luckett, R., Bazzett-Matabele, L., Ralefala, T.B., Monare, B., Nassali, M.N., Ramogola-Masire, D., Bvochora, M., Mitra, N., Wiebe, D. and Rebbeck, T.R. (2021). Clinical and sociodemographic factors associated with late stage cervical cancer diagnosis in Botswana. BMC Women’s Health, 21(1), 1–9.
  • Furumoto, H., & Irahara, M. (2002). Human papilloma virus (HPV) and cervical cancer. Journal of Medical Investigation, 49(3/4), 124–133.
  • Ghaleh, H. E. G., Shahriary, A., Izadi, M., & Farzanehpour, M. (2022). Advances in early diagnosis of cervical cancer based on biosensors. Biotechnology and Bioengineering, 119(9), 2305–2312.
  • Guimarães, Y. M., Godoy, L. R., Longatto-Filho, A., & Reis, R. D. (2022). Management of early-stage cervical cancer: A literature review. Cancers, 14(3), 575.
  • Gupta, A.K., Lee, J.H., Wilke, W.W., Quon, H., Smith, G., Maity, A., Buatti, J.M. and Spitz, D.R. (2009). Radiation response in two HPV-infected head-and-neck cancer cell lines in comparison to a non–HPV-infected cell line and relationship to signaling through AKT. International Journal of Radiation Oncology* Biology* Physics, 74(3), 928–933.
  • Gupta, A., Shah, K., Oza, M. J., & Behl, T. (2019). Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 109, 484–492. https://doi.org/10.1016/j.biopha.2018.10.155
  • Ha, S. K., Moon, E., Ju, M. S., Kim, D. H., Ryu, J. H., Oh, M. S., & Kim, S. Y. (2012). 6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection. Neuropharmacology, 63(2), 211–223.
  • Hay, N., & Sonenberg, N. (2004). Upstream and downstream of mTOR. Genes & Development, 18(16), 1926–1945.
  • Hopkins, A. L. (2008). Network pharmacology: The next paradigm in drug discovery. Nature Chemical Biology, 4(11), 682–690.
  • Hoter, A., El-Sabban, M. E., & Naim, H. Y. (2018). The HSP90 family: Structure, regulation, function, and implications in health and disease. International Journal of Molecular Sciences, 19(9), 2560.
  • Huang, C., Liu, L.Y., Li, Z.F., Wang, P., Ni, L., Song, L.P., Xu, D.H. and Song, T.S. (2008). Effects of small interfering RNAs targeting MAPK1 on gene expression profile in HeLa cells as revealed by microarray analysis. Cell Biology International, 32(9), 1081–1090.
  • Huang, Q., Matsuda, H., Sakai, K., Yamahara, J., & Tamai, Y. (1990). The effect of ginger on serotonin induced hypothermia and diarrhea. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan, 110(12), 936–942.
  • Jolad, S. D., Lantz, R. C., Chen, G. J., Bates, R. B., & Timmermann, B. N. (2005). Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochemistry, 66(13), 1614–1635.
  • Jolad, S. D., Lantz, R. C., Solyom, A. M., Chen, G. J., Bates, R. B., & Timmermann, B. N. (2004). Fresh organically grown ginger (Zingiber officinale): Composition and effects on LPS-induced PGE2 production. Phytochemistry, 65(13), 1937–1954.
  • Kesic, V. (2006). Management of cervical cancer. European Journal of Surgical Oncology (EJSO), 32(8), 832–837.
  • Keysar, S.B., Astling, D.P., Anderson, R.T., Vogler, B.W., Bowles, D.W., Morton, J.J., Paylor, J.J., Glogowska, M.J., Le, P.N., Eagles-Soukup, J.R. and Kako, S.L. (2013). A patient tumor transplant model of squamous cell cancer identifies PI3K inhibitors as candidate therapeutics in defined molecular bins. Molecular Oncology, 7(4), 776–790.
  • Kohrenhagen, N., Voelker, H. U., Schmidt, M., Kapp, M., Krockenberger, M., Frambach, T., … Kammerer, U. (2008). Expression of transketolase‐like 1 (TKTL1) and p‐Akt correlates with the progression of cervical neoplasia. Journal of Obstetrics and Gynaecology Research, 34(3), 293–300.
  • Kress, W. J., Prince, L. M., & Williams, K. J. (2002). The phylogeny and a new classification of the gingers (Zingiberaceae): Evidence from molecular data. American Journal of Botany, 89(10), 1682–1696.
  • Kulbe, H., Levinson, N. R., Balkwill, F., & Wilson, J. L. (2004). The chemokine network in cancer-much more than directing cell movement. The International Journal of Developmental Biology, 48(5-6), 489–496.
  • Kurmyshkina, O. V., Kovchur, P. I., & Volkova, T. O. (2015). Caspases as putative biomarkers of cervical cancer development. In Cell death-Autophagy, apoptosis and necrosis (pp. 267–297). INTECH.
  • Lantz, R. C., Chen, G. J., Sarihan, M., Solyom, A. M., Jolad, S. D., & Timmermann, B. N. (2007). The effect of extracts from ginger rhizome on inflammatory mediator production. Phytomedicine, 14(2–3), 123–128.
  • Le Goff, P., Montano, M. M., Schodin, D. J., & Katzenellenbogen, B. S. (1994). Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. Journal of Biological Chemistry, 269(6), 4458–4466.
  • Lechner, J. F., & Stoner, G. D. (2019). Gingers and their purified components as cancer chemopreventative agents. Molecules, 24, 2859. https://doi.org/10.3390/molecules24162859
  • Lee, H.S., Lee, I.H., Kang, K., Park, S.I., Jung, M., Yang, S.G., Kwon, T.W. and Lee, D.Y. (2021). A comprehensive understanding of the anticancer mechanisms of FDY2004 against cervical cancer based on network pharmacology. Natural Product Communications, 16(3), 1934578X211004304.
  • Lee, H. S., Lee, I. H., Kang, K., Park, S. I., Moon, S. J., Lee, C. H., & Lee, D. Y. (2021). A network pharmacology study on the molecular mechanisms of FDY003 for breast cancer treatment. Evidence-Based Complementary and Alternative Medicine, 2021. https://doi.org/10.1155/2021/3919143
  • Lee, E., & Surh, Y. J. (1998). Induction of apoptosis in HL-60 cells by pungent vanilloids,[6]-gingerol and [6]-paradol. Cancer Letters, 134(2), 163–168.
  • Lei, J., Ploner, A., Elfström, K. M., Wang, J., Roth, A., Fang, F., Sundström, K., Dillner, J., & Sparén, P. (2020). HPV vaccination and the risk of invasive cervical cancer. The New England Journal of Medicine, 383(14), 1340–1348.
  • Liang, T., He, Y., Chang, Y., & Liu, X. (2019). 6-shogaol a active component from ginger inhibits cell proliferation and induces apoptosis through inhibition of STAT-3 translocation in ovarian cancer cell lines (A2780). Biotechnology and Bioprocess Engineering, 24(3), 560–567.
  • Li, T. Y., & Chiang, B. H. (2017). 6-shogaol induces autophagic cell death then triggered apoptosis in colorectal adenocarcinoma HT-29 cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 93, 208–217. https://doi.org/10.1016/j.biopha.2017.06.038
  • Li, J., & Kurokawa, M. (2015). Regulation of MDM2 stability after DNA damage. Journal of Cellular Physiology, 230(10), 2318–2327.
  • Ling, L. R., & Wahab, A. (2005). Cytotoxic activity of selected Zingiberaceae. Malaysian Journal of Science, 24(1), 207–212.
  • Li, D. J., Shi, J., Jin, J., Du, N. Y., & He, Y. T. (2021). Epidemiological trend of cervical cancer. Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology], 43(9), 912–916.
  • Li, X., Tian, R., Gao, H., Yan, F., Ying, L., Yang, Y., Yang, P. and Gao, Y.E. (2018). Identification of significant gene signatures and prognostic biomarkers for patients with cervical cancer by integrated bioinformatic methods. Technology in Cancer Research & Treatment, 17, 1533033818767455.
  • Liu, Q., Peng, Y.-B., Zhou, P., Qi, L.-W., Zhang, M., Gao, N., Liu, E.-H., & Li, P. (2013). 6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α. Molecular Cancer, 12(1), 135. https://doi.org/10.1186/1476-4598-12-135
  • Li, L., Wang, L., You, Q. D., & Xu, X. L. (2019). Heat shock protein 90 inhibitors: An update on achievements, challenges, and future directions. Journal of Medicinal Chemistry, 63(5), 1798–1822.
  • Li, H., Wu, X., & Cheng, X. (2016). Advances in diagnosis and treatment of metastatic cervical cancer. Journal of Gynecologic Oncology, 27(4): e43.
  • Luo, T. T., Lu, Y., Yan, S. K., Xiao, X., Rong, X. L., & Guo, J. (2020). Network pharmacology in research of Chinese medicine formula: Methodology, application and prospective. Chinese Journal of Integrative Medicine, 26(1), 72–80.
  • Lv, J., & Li, L. (2019). Hub genes and key pathway identification in colorectal cancer based on bioinformatic analysis. BioMed Research International, 2019. https://doi.org/10.1155/2019/1545680.
  • Lwin, W. W., Park, K., Wauson, M., Gao, Q., Finn, P. W., Perkins, D., & Khanna, A. (2012). Systems biology approach to transplant tolerance: Proof of concept experiments using RNA interference (RNAi) to knock down hub genes in Jurkat and HeLa cells in vitro. Journal of Surgical Research, 176(1), e41–e46.
  • Ma, Y. Y., Wei, S. J., Lin, Y. C., Lung, J. C., Chang, T. C., Whang-Peng, J., … Shen, C. Y. (2000). PIK3CA as an oncogene in cervical cancer. Oncogene, 19(23), 2739–2744.
  • Miller, P. C., Clarke, J., Koru-Sengul, T., Brinkman, J., & El-Ashry, D. (2015). A novel MAPK–microRNA signature is predictive of hormone-therapy resistance and poor outcome in ER-positive breast CancerhMAPK–miRNA signature and hormone resistance. Clinical Cancer Research, 21(2), 373–385.
  • Morris, G. M., Huey, R., & Olson, A. J. (2008). Using autodock for ligand‐receptor docking. Current Protocols in Bioinformatics, 24(1), 8–14.
  • Niu, W. H., Wu, F., Cao, W. Y., Wu, Z. G., Chao, Y. C., Peng, F., & Liang, C. (2021). Network pharmacology for the identification of phytochemicals in traditional Chinese medicine for COVID-19 that may regulate interleukin-6. Bioscience Reports, 41(1), BSR20202583. https://doi.org/10.1042/BSR20202583.
  • Noor, F., Tahir Ul Qamar, M., Ashfaq, U. A., Albutti, A., Alwashmi, A. S., & Aljasir, M. A. (2022). Network pharmacology approach for medicinal plants: Review and assessment. Pharmaceuticals, 15(5), 572.
  • Obaidullah, A. J., Alanazi, M. M., Alsaif, N. A., Alanazi, A. S., Albassam, H., Az, A., … Tareq, A. M. (2022). Network pharmacology-and molecular docking-based identification of potential phytocompounds from Argyreia capitiformis in the treatment of inflammation. Evidence-Based Complementary and Alternative Medicine, 2022. https://doi.org/10.1155/2022/8037488
  • Olusola, P., Banerjee, H. N., Philley, J. V., & Dasgupta, S. (2019). Human papilloma virus-associated cervical cancer and health disparities. Cells, 8(6), 622.
  • Ordikhani, F., Erdem Arslan, M., Marcelo, R., Sahin, I., Grigsby, P., Schwarz, J. K., & Azab, A. K. (2016). Drug delivery approaches for the treatment of cervical cancer. Pharmaceutics, 8(3), 23.
  • Park, K. K., Chun, K. S., Lee, J. M., Lee, S. S., & Surh, Y. J. (1998). Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Letters, 129(2), 139–144.
  • Patel, H., Polanco-Echeverry, G., Segditsas, S., Volikos, E., McCart, A., Lai, C., Guenther, T., Zaitoun, A., Sieber, O., Ilyas, M., Northover, J., & Silver, A. (2007). Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma. International Journal of Cancer, 121(12), 2668–2673.
  • Pearce, A., Haas, M., Viney, R., Pearson, S. A., Haywood, P., Brown, C., & Ward, R. (2017). Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS One. 12(10), e0184360.
  • Pei, X. D., He, Z. L., Yao, H. L., Xiao, J. S., Li, L., Gu, J. Z., … Jiang, L. H. (2021). 6-Shogaol from ginger shows anti-tumor effect in cervical carcinoma via PI3K/Akt/mTOR pathway. European Journal of Nutrition, 60(5), 2781–2793.
  • Peter, K. V. (Ed.). (2006). Handbook of herbs and spices: volume 3. Woodhead Publishing.
  • Poornima, P., Kumar, J. D., Zhao, Q., Blunder, M., & Efferth, T. (2016). Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature. Pharmacological Research, 111, 290–302.
  • Reddy, M. N., Adnan, M., Alreshidi, M. M., Saeed, M., & Patel, M. (2020). Evaluation of anticancer, antibacterial and antioxidant properties of a medicinally treasured fern tectaria coadunata with its phytoconstituents analysis by HR-LCMS. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 20(15), 1845–1856.
  • Rhode, J., Fogoros, S., Zick, S., Wahl, H., Griffith, K. A., Huang, J., & Liu, J. R. (2007). Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complementary and Alternative Medicine, 7(1), 1–9.
  • Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498–2504. https://doi.org/10.1101/gr.1239303
  • Shukla, Y., & Singh, M. (2007). Cancer preventive properties of ginger: A brief review. Food and Chemical Toxicology, 45(5), 683–690.
  • Sirvent, A., Benistant, C., & Roche, S. (2012). Oncogenic signaling by tyrosine kinases of the SRC family in advanced colorectal cancer. American Journal of Cancer Research, 2(4), 357.
  • Soonthornthum, T., Arias-Pulido, H., Joste, N., Lomo, L., Muller, C., Rutledge, T., & Verschraegen, C. (2011). Epidermal growth factor receptor as a biomarker for cervical cancer. Annals of Oncology, 22(10), 2166–2178.
  • Stelzle, D., Tanaka, L. F., Lee, K. K., Khalil, A. I., Baussano, I., Shah, A. S., … Dalal, S. (2021). Estimates of the global burden of cervical cancer associated with HIV. The Lancet Global Health, 9(2), e161–e169.
  • Studio, D. (2008). Discovery studio. Accelrys [2.1].
  • Suekawa, M., Aburada, M., & Hosoya, E. (1986). Pharmacological studies on ginger. II. Pressor action of (6)-shogaol in anesthetized rats, or hindquarters, tail and mesenteric vascular beds of rats. Journal of Pharmacobio-Dynamics, 9(10), 842–852.
  • Suekawa, M., Ishige, A., Yuasa, K., Sudo, K., Aburada, M., & Hosoya, E. (1984). Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents,(6)-gingerol and (6)-shogaol. Journal of Pharmacobio-Dynamics, 7(11), 836–848.
  • Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249.
  • Surh, Y. J., Lee, E., & Lee, J. M. (1998). Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutation Research, 402(1–2), 259–267.
  • Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., Simonovic, M., Roth, A., Santos, A., Tsafou, K. P., Kuhn, M., Bork, P., Jensen, L. J., & von Mering, C. (2015). STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Research, 43(Database issue), D447–D452. https://doi.org/10.1093/nar/gku1003
  • Tan, B. S., Kang, O., Mai, C. W., Tiong, K. H., Khoo, A. S. B., Pichika, M. R., … Leong, C. O. (2013). 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ). Cancer Letters, 336(1), 127–139.
  • Tornatta, J. M., Carpenter, J. S., Schilder, J., & Cardenes, H. R. (2009). Representations of vaginal symptoms in cervical cancer survivors. Cancer Nursing, 32(5), 378–384.
  • Tuorkey, M. J. (2015). Cancer therapy with phytochemicals: Present and future perspectives. Biomedical and Environmental Sciences : BES, 28(11), 808–819. https://doi.org/10.3967/bes2015.112
  • van Schalkwyk, S. L., Maree, J. E., & Dreyer Wright, S. C. (2008). Cervical cancer: The route from signs and symptoms to treatment in South Africa. Reproductive Health Matters, 16(32), 9–17.
  • Wang, W., Corrigan-Cummins, M., Hudson, J., Maric, I., Simakova, O., Neelapu, S. S., … Calvo, K. R. (2012). MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response. haematologica, 97(4), 586.
  • Wu, B., & Xi, S. (2021). Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer. BMC Cancer, 21(1), 1–15.
  • Yarley, O. P. N., Kojo, A. B., Zhou, C., Yu, X., Gideon, A., Kwadwo, H. H., & Richard, O. (2021). Reviews on mechanisms of in vitro antioxidant, antibacterial and anticancer activities of water-soluble plant polysaccharides. International Journal of Biological Macromolecules, 183, 2262–2271.
  • Zhu, Y., Wang, L., Xu, L., & Ying, P. (2022). A network pharmacology study on the cervix prescription for treatment of cervical cancer. Journal of Immunology Research, 2022. https://doi.org/10.1155/2022/8945591
  • Zhu, Y., Warin, R. F., Soroka, D. N., Chen, H., & Sang, S. (2013). Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: Chemical synthesis and biological evaluation. PLoS One, 8(1), e54677. https://doi.org/10.1371/journal.pone.0054677
  • Zou, Q., Jin, J., Hu, H., Li, H. S., Romano, S., Xiao, Y., … Sun, S. C. (2014). USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nature Immunology, 15(6), 562–570.

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