Mechanism of Apoptosis Induction in Oral Cancer Cells by Uncaria-derived Flavonoids
Keywords:
Apoptosis, Oral cancer, Uncaria, flavonoids, oral cancer
Abstract
Introduction: Oral cancer is cancer that occurs in the oral cavity and oropharynx, ranking 16th as the most common cancer found with a number of new cases of 377,713 and a number of deaths of 177,757 cases in 2020. Several types of flavonoids contained in the genus Uncaria were found to have anticancer bioactivity, one of which is inducing apoptosis in oral cancer cells. Aim: This study aims to review the potential and mechanisms involved of flavonoids in inducing apoptosis in oral cancer cells. The literature review method was used in this study by conducting a systematic literature search on PubMed, ScienceDirect, and Google Scholar until October 2023. Results: A total of 13 studies were included in this study and our findings conclude that flavonoids, especially quercetin, kaempferol, rutin, umbelliferon, and epigallocatechin gallate (EGCG), have the potential to be used as anticancer agents, one of which has the ability to induce apoptosis, both through extrinsic and intrinsic pathway, in several oral cancer cell lines, including SCC-4, SCC-9, SCC-25, SAS, KB/VCR, Tca-8113, YD10B, YD38, MC-3, KB, and HSC-3, through the mechanism of inhibiting anti-apoptotic expression, activating pro-apoptotic protein expression, generating ROS, and regulating PI3K/AKT, MAPK, and JAK/STAT signaling pathways. Conclusion: We conclude that Uncaria-derived flavonoids hav the potential to induce apoptosis, both extrinsic and intrinsic, in oral cancer cells.
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References
Abdullah, N. H., Salim, F., & Ahmad, R. (2016). Isolation of Flavonols from the Stems of Malaysian Uncaria cordata var. ferruginea (Blume) Ridsd. Malaysian Journal of Analytical Science, 20(4), 844–848. https://doi.org/10.17576/mjas-2016-2004-18
Abotaleb, M., Samuel, S., Varghese, E., Varghese, S., Kubatka, P., Liskova, A., & Büsselberg, D. (2018). Flavonoids in Cancer and Apoptosis. Cancers, 11(1), 28. https://doi.org/10.3390/cancers11010028
Aggarwal, S., John, S., Sapra, L., Sharma, S. C., & Das, S. N. (2019). Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells. Cancer Chemotherapy and Pharmacology, 83(3), 451–461. https://doi.org/10.1007/s00280-018-3746-x
Alfani, N. R., Febrianti, R., & Amananti, W. (2023). Analysis of Total Flavonoid Content in the Extract of Bajakah Kalalawit Root (Uncaria gambir Roxb) Infunded Results. Indonesian Journal of Chemical Science and Technology (IJCST), 6(1), 65. https://doi.org/10.24114/ijcst.v6i1.43184
Barazzuol, L., Coppes, R. P., & van Luijk, P. (2020). Prevention and treatment of radiotherapy‐induced side effects. Molecular Oncology, 14(7), 1538–1554. https://doi.org/10.1002/1878-0261.12750
Blackadar, C. B. (2016). Historical review of the causes of cancer. World Journal of Clinical Oncology, 7(1), 54. https://doi.org/10.5306/wjco.v7.i1.54
Coutinho-Camillo, C. M., Lourenço, S. V., Puga, R. D., Damascena, A. S., Teshima, T. H. N., Kowalski, L. P., & Soares, F. A. (2017). Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases. Applied Cancer Research, 37(1), 2. https://doi.org/10.1186/s41241-016-0008-2
Dwivedi, R., Pandey, R., Chandra, S., & Mehrotra, D. (2020). Apoptosis and genes involved in oral cancer - a comprehensive review. Oncology Reviews, 14(2). https://doi.org/10.4081/oncol.2020.472
Feller, L., & Lemmer, J. (2012). Oral Squamous Cell Carcinoma: Epidemiology, Clinical Presentation and Treatment. Journal of Cancer Therapy, 03(04), 263–268. https://doi.org/10.4236/jct.2012.34037
Fernando, J., & Jones, R. (2015). The principles of cancer treatment by chemotherapy. Surgery (Oxford), 33(3), 131–135. https://doi.org/10.1016/j.mpsur.2015.01.005
Fragoso, R., & Barata, J. T. (2015). Kinases, tails and more: Regulation of PTEN function by phosphorylation. Methods, 77–78, 75–81. https://doi.org/10.1016/j.ymeth.2014.10.015
Hague, A., Eveson, J. W., MacFarlane, M., Huntley, S., Janghra, N., & Thavaraj, S. (2004). Caspase-3 expression is reduced, in the absence of cleavage, in terminally differentiated normal oral epithelium but is increased in oral squamous cell carcinomas and correlates with tumour stage. The Journal of Pathology, 204(2), 175–182. https://doi.org/10.1002/path.1630
He, S., Chakraborty, R., & Ranganathan, S. (2022). Proliferation and Apoptosis Pathways and Factors in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, 23(3), 1562. https://doi.org/10.3390/ijms23031562
Huang, C.-F., Liu, S.-H., Ho, T.-J., Lee, K.-I., Fang, K.-M., Lo, W.-C., Liu, J.-M., Wu, C.-C., & Su, C.-C. (2022). Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation regulated ERK/GSK 3α/β mediated mitochondria dependent apoptotic signaling pathway. Oncology Letters, 23(3), 78. https://doi.org/10.3892/ol.2022.13198
Huang, Y.-C., Sung, M.-Y., Lin, T.-K., Kuo, C.-Y., & Hsu, Y.-C. (2023). Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer. Journal of the Formosan Medical Association. https://doi.org/10.1016/j.jfma.2023.10.009
Irani, S. (2020). New insights into oral cancer—Risk factors and prevention: A review of literature. International Journal of Preventive Medicine, 11(1), 202. https://doi.org/10.4103/ijpvm.IJPVM_403_18
Jain, M., Kasetty, S., Udyavara Sridhara, S., Jain, N., Khan, S., & Desai, A. (2013). Apoptosis and Its Significance in Oral Diseases: An Update. Journal of Oral Diseases, 2013, 1–11. https://doi.org/10.1155/2013/401049
Jeon, S.-J., Jung, G.-H., Choi, E.-Y., Han, E.-J., Lee, J.-H., Han, S.-H., Woo, J.-S., Jung, S.-H., & Jung, J.-Y. (2023). Kaempferol induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in MC-3 cells. Toxicological Research. https://doi.org/10.1007/s43188-023-00206-z
Karak, P. (2019). Biological activities of flavonoids: An overview. Int. J. Pharm. Sci. Res, 10(4), 1567–1574. https://doi.org/http://dx.doi.org/10.13040/IJPSR.0975-8232.10(4).1567-74
Kawashita, Y., Soutome, S., Umeda, M., & Saito, T. (2020). Oral management strategies for radiotherapy of head and neck cancer. Japanese Dental Science Review, 56(1), 62–67. https://doi.org/10.1016/j.jdsr.2020.02.001
Khan, H., Ullah, H., Martorell, M., Valdes, S. E., Belwal, T., Tejada, S., Sureda, A., & Kamal, M. A. (2021). Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Seminars in Cancer Biology, 69, 200–211. https://doi.org/https://doi.org/10.1016/j.semcancer.2019.07.023
Kim, C.-D., Cha, J.-D., Li, S., & Cha, I.-H. (2015). The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma. Archives of Oral Biology, 60(9), 1283–1298. https://doi.org/10.1016/j.archoralbio.2015.05.009
Kolodziejczyk-Czepas, J., Ponczek, M., Sady-Janczak, M., Pilarski, R., & Bukowska, B. (2021). Extracts from Uncaria tomentosa as antiplatelet agents and thrombin inhibitors – The in vitro and in silico study. Journal of Ethnopharmacology, 267, 113494. https://doi.org/10.1016/j.jep.2020.113494
Kopustinskiene, D. M., Jakstas, V., Savickas, A., & Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12(2), 457. https://doi.org/10.3390/nu12020457
Lai, W.-W., Hsu, S.-C., Chueh, F.-S., Chen, Y.-Y., Yang, J.-S., Lin, J.-P., Lien, J.-C., Tsai, C.-H., & Chung, J.-G. (2013). Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Research, 33(5), 1941–1950.
Lanfei, X., Jiping, G. A. O., Xiaoru, Y. A. N., Xiaotang, W., & Guohua, X. U. G. and S. (2021). Effect of quercetin on cell proliferation, migration, and invasion and PI3K / AKT signaling pathway regulation in the oral cancer cell line Tca-8113. 中国比较医学杂志（英文版）, 31(6), 30–34. https://doi.org/10.3969/j.issn.1671-7856.2021.06.005
Leelahavanichkul, K., Amornphimoltham, P., Molinolo, A. A., Basile, J. R., Koontongkaew, S., & Gutkind, J. S. (2014). A role for p38 MAPK in head and neck cancer cell growth and tumor‐induced angiogenesis and lymphangiogenesis. Molecular Oncology, 8(1), 105–118. https://doi.org/10.1016/j.molonc.2013.10.003
Lee, T. K., Park, C., Jeong, S., Jeong, M., Kim, G., Kim, W., & Choi, Y. H. (2016). Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway. Drug Development Research, 77(5), 227–240. https://doi.org/10.1002/ddr.21315
Liang, J.-H., Wang, C., Huo, X.-K., Tian, X.-G., Zhao, W.-Y., Wang, X., Sun, C.-P., & Ma, X.-C. (2020). The genus Uncaria: A review on phytochemical metabolites and biological aspects. Fitoterapia, 147, 104772. https://doi.org/10.1016/j.fitote.2020.104772
Lin, C.-W., Chen, P.-N., Chen, M.-K., Yang, W.-E., Tang, C.-H., Yang, S.-F., & Hsieh, Y.-S. (2013). Kaempferol Reduces Matrix Metalloproteinase-2 Expression by Down-Regulating ERK1/2 and the Activator Protein-1 Signaling Pathways in Oral Cancer Cells. PLoS ONE, 8(11), e80883. https://doi.org/10.1371/journal.pone.0080883
Ma, Y., Yao, C., Liu, H., Yu, F., Lin, J., Lu, K., Liao, C., Chueh, F., & Chung, J. (2018). Quercetin induced apoptosis of human oral cancer SAS cells through mitochondria and endoplasmic reticulum mediated signaling pathways. Oncology Letters. https://doi.org/10.3892/ol.2018.8584
Miloro, M., Ghali, G. E., Larsen, P. E., & Waite, P. D. (2011). Peterson’s Principles of Oral and Maxillofacial Surgery (3rd ed.). People’s Medical Publishing House.
Misra, A., Rai, S., & Misra, D. (2016). Functional role of apoptosis in oral diseases: An update. Journal of Oral and Maxillofacial Pathology, 20(3), 491. https://doi.org/10.4103/0973-029X.190953
Mosaddad, S. A., Beigi, K., Doroodizadeh, T., Haghnegahdar, M., Golfeshan, F., Ranjbar, R., & Tebyanian, H. (2021). Therapeutic applications of herbal/synthetic/bio-drug in oral cancer: An update. European Journal of Pharmacology, 890, 173657. https://doi.org/10.1016/j.ejphar.2020.173657
Nandini, D. B., Rao, Roopa. S., Hosmani, J., Khan, S., Patil, S., & Awan, K. H. (2020). Novel therapies in the management of oral cancer: An update. Disease-a-Month, 66(12), 101036. https://doi.org/10.1016/j.disamonth.2020.101036
Neagu, M., Constantin, C., Popescu, I. D., Zipeto, D., Tzanakakis, G., Nikitovic, D., Fenga, C., Stratakis, C. A., Spandidos, D. A., & Tsatsakis, A. M. (2019). Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player. Frontiers in Oncology, 9. https://doi.org/10.3389/fonc.2019.00348
Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: an overview. Journal of Nutritional Science, 5, e47. https://doi.org/10.1017/jns.2016.41
Peng, Q., Deng, Z., Pan, H., Gu, L., Liu, O., & Tang, Z. (2017). Mitogen-activated protein kinase signaling pathway in oral cancer (Review). Oncology Letters. https://doi.org/10.3892/ol.2017.7491
Petti, S. (2009). Lifestyle risk factors for oral cancer. Oral Oncology, 45(4–5), 340–350. https://doi.org/10.1016/j.oraloncology.2008.05.018
Pfeffer, C., & Singh, A. (2018). Apoptosis: A Target for Anticancer Therapy. International Journal of Molecular Sciences, 19(2), 448. https://doi.org/10.3390/ijms19020448
Raffa, D., Maggio, B., Raimondi, M. V., Plescia, F., & Daidone, G. (2017). Recent discoveries of anticancer flavonoids. European Journal of Medicinal Chemistry, 142, 213–228. https://doi.org/10.1016/j.ejmech.2017.07.034
Rahaman, S. T., & Mondal, S. (2020). Flavonoids: A vital resource in healthcare and medicine. Pharmacy & Pharmacology International Journal, 8(2), 91–104. https://doi.org/10.15406/ppij.2020.08.00285
Ridho, F. M. (2020). Kandungan Metabolit Sekunder dari Ekstrak Kayu Bajakah (Uncaria nervosa Elmer) dan Bioaktivitasnya Sebagai Antikanker [Universitas Airlangga]. http://lib.unair.ac.id
Ridho, F. M. (2023). Mechanism of Alkaloids and Flavonoids in Bajakah (Uncaria nervosa Elmer) as Antidiabetic Agents. Jurnal Ilmu Medis Indonesia, 3(1), 9–16. https://doi.org/10.35912/jimi.v3i1.2296
Saad, M. F. M., Goh, H.-H., Rajikan, R., Yusof, T. R. T., Baharum, S. N., & Bunawan, H. (2020). Uncaria gambir (W. Hunter) Roxb: From phytochemical composition to pharmacological importance. Tropical Journal of Pharmaceutical Research, 19(8), 1767–1773. https://doi.org/10.4314/tjpr.v19i8.28
Sari, L. M. (2018). Apoptosis: mekanisme molekuler kematian sel. Cakradonya Dent J, 10(2), 65–70.
Scully, C., & Bagan, J. (2009). Oral squamous cell carcinoma overview. Oral Oncology, 45(4–5), 301–308. https://doi.org/10.1016/j.oraloncology.2009.01.004
Sharifi, S., Barar, J., Hejazi, M. S., & Samadi, N. (2014). Roles of the Bcl-2/Bax Ratio, Caspase-8 and 9 in Resistance of Breast Cancer Cells to Paclitaxel. Asian Pacific Journal of Cancer Prevention, 15(20), 8617–8622. https://doi.org/10.7314/APJCP.2014.15.20.8617
Sinevici, N., & O’sullivan, J. (2016). Oral cancer: Deregulated molecular events and their use as biomarkers. Oral Oncology, 61, 12–18. https://doi.org/10.1016/j.oraloncology.2016.07.013
Singh, M., & Bagewadi, A. (2022). Management of oral mucositis caused by radiotherapy – A comprehensive review. SRM Journal of Research in Dental Sciences, 13(2), 68. https://doi.org/10.4103/srmjrds.srmjrds_31_22
Son, H.-K., & Kim, D. (2023). Quercetin Induces Cell Cycle Arrest and Apoptosis in YD10B and YD38 Oral Squamous Cell Carcinoma Cells. Asian Pacific Journal of Cancer Prevention : APJCP, 24(1), 283–289. https://doi.org/10.31557/APJCP.2023.24.1.283
Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A.-H., & Jaremko, M. (2020). Important Flavonoids and Their Role as a Therapeutic Agent. Molecules, 25(22), 5243. https://doi.org/10.3390/molecules25225243
van den Boogaard, W. M. C., Komninos, D. S. J., & Vermeij, W. P. (2022). Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers, 14(3), 627. https://doi.org/10.3390/cancers14030627
Veeravarmal, V., Austin, R., Siddavaram, N., Thiruneelakandan, S., & Nassar, M. M. (2016). Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma. Journal of Oral and Maxillofacial Pathology, 20(3), 445. https://doi.org/10.4103/0973-029X.190947
World Health Organization. (2020). Oral Health. https://gco.iarc.fr/today/data/factsheets/cancers/1-Lip-oral-cavity-fact-sheet.pdf
Yuan, Z., Wang, H., Hu, Z., Huang, Y., Yao, F., Sun, S., & Wu, B. (2015). Quercetin Inhibits Proliferation and Drug Resistance in KB/VCR Oral Cancer Cells and Enhances Its Sensitivity to Vincristine. Nutrition and Cancer, 67(1), 126–136. https://doi.org/10.1080/01635581.2015.965334
Yue, J., & López, J. M. (2020). Understanding MAPK Signaling Pathways in Apoptosis. International Journal of Molecular Sciences, 21(7), 2346. https://doi.org/10.3390/ijms21072346
Zhang, Q., Zhao, J. J., Xu, J., Feng, F., & Qu, W. (2015). Medicinal uses, phytochemistry and pharmacology of the genus Uncaria. Journal of Ethnopharmacology, 173, 48–80. https://doi.org/10.1016/j.jep.2015.06.011
Zhang, R., Li, G., Zhang, Q., Tang, Q., Huang, J., Hu, C., Liu, Y., Wang, Q., Liu, W., Gao, N., & Zhou, S. (2018). Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells. Cell Death & Disease, 9(6), 598. https://doi.org/10.1038/s41419-018-0641-7
Zhao, L., Lin, H., Chen, S., Chen, S., Cui, M., Shi, D., Wang, B., Ma, K., & Shao, Z. (2018). Hydrogen peroxide induces programmed necrosis in rat nucleus pulposus cells through the RIP1/RIP3‐PARP‐AIF pathway. Journal of Orthopaedic Research, 36(4), 1269–1282. https://doi.org/10.1002/jor.23751
Zughaibi, T. A., Suhail, M., Tarique, M., & Tabrez, S. (2021). Targeting PI3K/Akt/mTOR Pathway by Different Flavonoids: A Cancer Chemopreventive Approach. International Journal of Molecular Sciences, 22(22), 12455. https://doi.org/10.3390/ijms222212455
Abotaleb, M., Samuel, S., Varghese, E., Varghese, S., Kubatka, P., Liskova, A., & Büsselberg, D. (2018). Flavonoids in Cancer and Apoptosis. Cancers, 11(1), 28. https://doi.org/10.3390/cancers11010028
Aggarwal, S., John, S., Sapra, L., Sharma, S. C., & Das, S. N. (2019). Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells. Cancer Chemotherapy and Pharmacology, 83(3), 451–461. https://doi.org/10.1007/s00280-018-3746-x
Alfani, N. R., Febrianti, R., & Amananti, W. (2023). Analysis of Total Flavonoid Content in the Extract of Bajakah Kalalawit Root (Uncaria gambir Roxb) Infunded Results. Indonesian Journal of Chemical Science and Technology (IJCST), 6(1), 65. https://doi.org/10.24114/ijcst.v6i1.43184
Barazzuol, L., Coppes, R. P., & van Luijk, P. (2020). Prevention and treatment of radiotherapy‐induced side effects. Molecular Oncology, 14(7), 1538–1554. https://doi.org/10.1002/1878-0261.12750
Blackadar, C. B. (2016). Historical review of the causes of cancer. World Journal of Clinical Oncology, 7(1), 54. https://doi.org/10.5306/wjco.v7.i1.54
Coutinho-Camillo, C. M., Lourenço, S. V., Puga, R. D., Damascena, A. S., Teshima, T. H. N., Kowalski, L. P., & Soares, F. A. (2017). Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases. Applied Cancer Research, 37(1), 2. https://doi.org/10.1186/s41241-016-0008-2
Dwivedi, R., Pandey, R., Chandra, S., & Mehrotra, D. (2020). Apoptosis and genes involved in oral cancer - a comprehensive review. Oncology Reviews, 14(2). https://doi.org/10.4081/oncol.2020.472
Feller, L., & Lemmer, J. (2012). Oral Squamous Cell Carcinoma: Epidemiology, Clinical Presentation and Treatment. Journal of Cancer Therapy, 03(04), 263–268. https://doi.org/10.4236/jct.2012.34037
Fernando, J., & Jones, R. (2015). The principles of cancer treatment by chemotherapy. Surgery (Oxford), 33(3), 131–135. https://doi.org/10.1016/j.mpsur.2015.01.005
Fragoso, R., & Barata, J. T. (2015). Kinases, tails and more: Regulation of PTEN function by phosphorylation. Methods, 77–78, 75–81. https://doi.org/10.1016/j.ymeth.2014.10.015
Hague, A., Eveson, J. W., MacFarlane, M., Huntley, S., Janghra, N., & Thavaraj, S. (2004). Caspase-3 expression is reduced, in the absence of cleavage, in terminally differentiated normal oral epithelium but is increased in oral squamous cell carcinomas and correlates with tumour stage. The Journal of Pathology, 204(2), 175–182. https://doi.org/10.1002/path.1630
He, S., Chakraborty, R., & Ranganathan, S. (2022). Proliferation and Apoptosis Pathways and Factors in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, 23(3), 1562. https://doi.org/10.3390/ijms23031562
Huang, C.-F., Liu, S.-H., Ho, T.-J., Lee, K.-I., Fang, K.-M., Lo, W.-C., Liu, J.-M., Wu, C.-C., & Su, C.-C. (2022). Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation regulated ERK/GSK 3α/β mediated mitochondria dependent apoptotic signaling pathway. Oncology Letters, 23(3), 78. https://doi.org/10.3892/ol.2022.13198
Huang, Y.-C., Sung, M.-Y., Lin, T.-K., Kuo, C.-Y., & Hsu, Y.-C. (2023). Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer. Journal of the Formosan Medical Association. https://doi.org/10.1016/j.jfma.2023.10.009
Irani, S. (2020). New insights into oral cancer—Risk factors and prevention: A review of literature. International Journal of Preventive Medicine, 11(1), 202. https://doi.org/10.4103/ijpvm.IJPVM_403_18
Jain, M., Kasetty, S., Udyavara Sridhara, S., Jain, N., Khan, S., & Desai, A. (2013). Apoptosis and Its Significance in Oral Diseases: An Update. Journal of Oral Diseases, 2013, 1–11. https://doi.org/10.1155/2013/401049
Jeon, S.-J., Jung, G.-H., Choi, E.-Y., Han, E.-J., Lee, J.-H., Han, S.-H., Woo, J.-S., Jung, S.-H., & Jung, J.-Y. (2023). Kaempferol induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in MC-3 cells. Toxicological Research. https://doi.org/10.1007/s43188-023-00206-z
Karak, P. (2019). Biological activities of flavonoids: An overview. Int. J. Pharm. Sci. Res, 10(4), 1567–1574. https://doi.org/http://dx.doi.org/10.13040/IJPSR.0975-8232.10(4).1567-74
Kawashita, Y., Soutome, S., Umeda, M., & Saito, T. (2020). Oral management strategies for radiotherapy of head and neck cancer. Japanese Dental Science Review, 56(1), 62–67. https://doi.org/10.1016/j.jdsr.2020.02.001
Khan, H., Ullah, H., Martorell, M., Valdes, S. E., Belwal, T., Tejada, S., Sureda, A., & Kamal, M. A. (2021). Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Seminars in Cancer Biology, 69, 200–211. https://doi.org/https://doi.org/10.1016/j.semcancer.2019.07.023
Kim, C.-D., Cha, J.-D., Li, S., & Cha, I.-H. (2015). The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma. Archives of Oral Biology, 60(9), 1283–1298. https://doi.org/10.1016/j.archoralbio.2015.05.009
Kolodziejczyk-Czepas, J., Ponczek, M., Sady-Janczak, M., Pilarski, R., & Bukowska, B. (2021). Extracts from Uncaria tomentosa as antiplatelet agents and thrombin inhibitors – The in vitro and in silico study. Journal of Ethnopharmacology, 267, 113494. https://doi.org/10.1016/j.jep.2020.113494
Kopustinskiene, D. M., Jakstas, V., Savickas, A., & Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12(2), 457. https://doi.org/10.3390/nu12020457
Lai, W.-W., Hsu, S.-C., Chueh, F.-S., Chen, Y.-Y., Yang, J.-S., Lin, J.-P., Lien, J.-C., Tsai, C.-H., & Chung, J.-G. (2013). Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Research, 33(5), 1941–1950.
Lanfei, X., Jiping, G. A. O., Xiaoru, Y. A. N., Xiaotang, W., & Guohua, X. U. G. and S. (2021). Effect of quercetin on cell proliferation, migration, and invasion and PI3K / AKT signaling pathway regulation in the oral cancer cell line Tca-8113. 中国比较医学杂志（英文版）, 31(6), 30–34. https://doi.org/10.3969/j.issn.1671-7856.2021.06.005
Leelahavanichkul, K., Amornphimoltham, P., Molinolo, A. A., Basile, J. R., Koontongkaew, S., & Gutkind, J. S. (2014). A role for p38 MAPK in head and neck cancer cell growth and tumor‐induced angiogenesis and lymphangiogenesis. Molecular Oncology, 8(1), 105–118. https://doi.org/10.1016/j.molonc.2013.10.003
Lee, T. K., Park, C., Jeong, S., Jeong, M., Kim, G., Kim, W., & Choi, Y. H. (2016). Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway. Drug Development Research, 77(5), 227–240. https://doi.org/10.1002/ddr.21315
Liang, J.-H., Wang, C., Huo, X.-K., Tian, X.-G., Zhao, W.-Y., Wang, X., Sun, C.-P., & Ma, X.-C. (2020). The genus Uncaria: A review on phytochemical metabolites and biological aspects. Fitoterapia, 147, 104772. https://doi.org/10.1016/j.fitote.2020.104772
Lin, C.-W., Chen, P.-N., Chen, M.-K., Yang, W.-E., Tang, C.-H., Yang, S.-F., & Hsieh, Y.-S. (2013). Kaempferol Reduces Matrix Metalloproteinase-2 Expression by Down-Regulating ERK1/2 and the Activator Protein-1 Signaling Pathways in Oral Cancer Cells. PLoS ONE, 8(11), e80883. https://doi.org/10.1371/journal.pone.0080883
Ma, Y., Yao, C., Liu, H., Yu, F., Lin, J., Lu, K., Liao, C., Chueh, F., & Chung, J. (2018). Quercetin induced apoptosis of human oral cancer SAS cells through mitochondria and endoplasmic reticulum mediated signaling pathways. Oncology Letters. https://doi.org/10.3892/ol.2018.8584
Miloro, M., Ghali, G. E., Larsen, P. E., & Waite, P. D. (2011). Peterson’s Principles of Oral and Maxillofacial Surgery (3rd ed.). People’s Medical Publishing House.
Misra, A., Rai, S., & Misra, D. (2016). Functional role of apoptosis in oral diseases: An update. Journal of Oral and Maxillofacial Pathology, 20(3), 491. https://doi.org/10.4103/0973-029X.190953
Mosaddad, S. A., Beigi, K., Doroodizadeh, T., Haghnegahdar, M., Golfeshan, F., Ranjbar, R., & Tebyanian, H. (2021). Therapeutic applications of herbal/synthetic/bio-drug in oral cancer: An update. European Journal of Pharmacology, 890, 173657. https://doi.org/10.1016/j.ejphar.2020.173657
Nandini, D. B., Rao, Roopa. S., Hosmani, J., Khan, S., Patil, S., & Awan, K. H. (2020). Novel therapies in the management of oral cancer: An update. Disease-a-Month, 66(12), 101036. https://doi.org/10.1016/j.disamonth.2020.101036
Neagu, M., Constantin, C., Popescu, I. D., Zipeto, D., Tzanakakis, G., Nikitovic, D., Fenga, C., Stratakis, C. A., Spandidos, D. A., & Tsatsakis, A. M. (2019). Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player. Frontiers in Oncology, 9. https://doi.org/10.3389/fonc.2019.00348
Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: an overview. Journal of Nutritional Science, 5, e47. https://doi.org/10.1017/jns.2016.41
Peng, Q., Deng, Z., Pan, H., Gu, L., Liu, O., & Tang, Z. (2017). Mitogen-activated protein kinase signaling pathway in oral cancer (Review). Oncology Letters. https://doi.org/10.3892/ol.2017.7491
Petti, S. (2009). Lifestyle risk factors for oral cancer. Oral Oncology, 45(4–5), 340–350. https://doi.org/10.1016/j.oraloncology.2008.05.018
Pfeffer, C., & Singh, A. (2018). Apoptosis: A Target for Anticancer Therapy. International Journal of Molecular Sciences, 19(2), 448. https://doi.org/10.3390/ijms19020448
Raffa, D., Maggio, B., Raimondi, M. V., Plescia, F., & Daidone, G. (2017). Recent discoveries of anticancer flavonoids. European Journal of Medicinal Chemistry, 142, 213–228. https://doi.org/10.1016/j.ejmech.2017.07.034
Rahaman, S. T., & Mondal, S. (2020). Flavonoids: A vital resource in healthcare and medicine. Pharmacy & Pharmacology International Journal, 8(2), 91–104. https://doi.org/10.15406/ppij.2020.08.00285
Ridho, F. M. (2020). Kandungan Metabolit Sekunder dari Ekstrak Kayu Bajakah (Uncaria nervosa Elmer) dan Bioaktivitasnya Sebagai Antikanker [Universitas Airlangga]. http://lib.unair.ac.id
Ridho, F. M. (2023). Mechanism of Alkaloids and Flavonoids in Bajakah (Uncaria nervosa Elmer) as Antidiabetic Agents. Jurnal Ilmu Medis Indonesia, 3(1), 9–16. https://doi.org/10.35912/jimi.v3i1.2296
Saad, M. F. M., Goh, H.-H., Rajikan, R., Yusof, T. R. T., Baharum, S. N., & Bunawan, H. (2020). Uncaria gambir (W. Hunter) Roxb: From phytochemical composition to pharmacological importance. Tropical Journal of Pharmaceutical Research, 19(8), 1767–1773. https://doi.org/10.4314/tjpr.v19i8.28
Sari, L. M. (2018). Apoptosis: mekanisme molekuler kematian sel. Cakradonya Dent J, 10(2), 65–70.
Scully, C., & Bagan, J. (2009). Oral squamous cell carcinoma overview. Oral Oncology, 45(4–5), 301–308. https://doi.org/10.1016/j.oraloncology.2009.01.004
Sharifi, S., Barar, J., Hejazi, M. S., & Samadi, N. (2014). Roles of the Bcl-2/Bax Ratio, Caspase-8 and 9 in Resistance of Breast Cancer Cells to Paclitaxel. Asian Pacific Journal of Cancer Prevention, 15(20), 8617–8622. https://doi.org/10.7314/APJCP.2014.15.20.8617
Sinevici, N., & O’sullivan, J. (2016). Oral cancer: Deregulated molecular events and their use as biomarkers. Oral Oncology, 61, 12–18. https://doi.org/10.1016/j.oraloncology.2016.07.013
Singh, M., & Bagewadi, A. (2022). Management of oral mucositis caused by radiotherapy – A comprehensive review. SRM Journal of Research in Dental Sciences, 13(2), 68. https://doi.org/10.4103/srmjrds.srmjrds_31_22
Son, H.-K., & Kim, D. (2023). Quercetin Induces Cell Cycle Arrest and Apoptosis in YD10B and YD38 Oral Squamous Cell Carcinoma Cells. Asian Pacific Journal of Cancer Prevention : APJCP, 24(1), 283–289. https://doi.org/10.31557/APJCP.2023.24.1.283
Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A.-H., & Jaremko, M. (2020). Important Flavonoids and Their Role as a Therapeutic Agent. Molecules, 25(22), 5243. https://doi.org/10.3390/molecules25225243
van den Boogaard, W. M. C., Komninos, D. S. J., & Vermeij, W. P. (2022). Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers, 14(3), 627. https://doi.org/10.3390/cancers14030627
Veeravarmal, V., Austin, R., Siddavaram, N., Thiruneelakandan, S., & Nassar, M. M. (2016). Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma. Journal of Oral and Maxillofacial Pathology, 20(3), 445. https://doi.org/10.4103/0973-029X.190947
World Health Organization. (2020). Oral Health. https://gco.iarc.fr/today/data/factsheets/cancers/1-Lip-oral-cavity-fact-sheet.pdf
Yuan, Z., Wang, H., Hu, Z., Huang, Y., Yao, F., Sun, S., & Wu, B. (2015). Quercetin Inhibits Proliferation and Drug Resistance in KB/VCR Oral Cancer Cells and Enhances Its Sensitivity to Vincristine. Nutrition and Cancer, 67(1), 126–136. https://doi.org/10.1080/01635581.2015.965334
Yue, J., & López, J. M. (2020). Understanding MAPK Signaling Pathways in Apoptosis. International Journal of Molecular Sciences, 21(7), 2346. https://doi.org/10.3390/ijms21072346
Zhang, Q., Zhao, J. J., Xu, J., Feng, F., & Qu, W. (2015). Medicinal uses, phytochemistry and pharmacology of the genus Uncaria. Journal of Ethnopharmacology, 173, 48–80. https://doi.org/10.1016/j.jep.2015.06.011
Zhang, R., Li, G., Zhang, Q., Tang, Q., Huang, J., Hu, C., Liu, Y., Wang, Q., Liu, W., Gao, N., & Zhou, S. (2018). Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells. Cell Death & Disease, 9(6), 598. https://doi.org/10.1038/s41419-018-0641-7
Zhao, L., Lin, H., Chen, S., Chen, S., Cui, M., Shi, D., Wang, B., Ma, K., & Shao, Z. (2018). Hydrogen peroxide induces programmed necrosis in rat nucleus pulposus cells through the RIP1/RIP3‐PARP‐AIF pathway. Journal of Orthopaedic Research, 36(4), 1269–1282. https://doi.org/10.1002/jor.23751
Zughaibi, T. A., Suhail, M., Tarique, M., & Tabrez, S. (2021). Targeting PI3K/Akt/mTOR Pathway by Different Flavonoids: A Cancer Chemopreventive Approach. International Journal of Molecular Sciences, 22(22), 12455. https://doi.org/10.3390/ijms222212455
Published
2023-12-31
How to Cite
Ridho, F. M., Iqbal, M., Agustina, A. W., & Syachputra, A. J. (2023). Mechanism of Apoptosis Induction in Oral Cancer Cells by Uncaria-derived Flavonoids. Ad-Dawaa’ Journal of Pharmaceutical Sciences, 6(2), 127-144. https://doi.org/10.24252/djps.v6i2.42944
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