Phytochemicals in Cancer Treatment : A Review
Abstract
Cancer is a heterogeneous disease characterized by uncontrolled proliferation and impaired
cell cycle leading to the growth of abnormal cells that invade and metastasize to other parts of the body. Oxidative stress, hypoxia, genetic mutations and lack of apoptotic function are the main internal causes of cancer, whereas the external causes are related to increased exposure to stress, pollution, smoking, radiation and ultraviolet rays. Phytochemicals derived from plants, serve as vital resources for novel drugs and are also sources for cancer therapy. The objective of this review is to describe the active compounds derived from the natural products/plants, along with their pharmacologic action and molecular targets.
Keywords:
Cancer, Phytochemicals, Oxidative stressDOI
https://doi.org/10.22270/jddt.v10i3.4075References
Bhatt AP, Redinbo MR, Bultman SJ ,The role of the microbiomein cancer development and therapy,Acancer journal for Clinicians,2017;67(4):326-344.2.Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM , Howlader N, Henley SJ , Anderson RN, Firth AU, Ma J, Kohler BA, Jemal A , Annual Report to the Nation on the Status of Cancer, part I: national cancer statistics, Cancer, 2018 ;124:2785–2800.3.Vineis P, Wild CP,Global cancer patterns: causes and prevention, Lancet,2012; 383:549–5574.Baskar A, Lee KA, Yeo R, Yeoh KW, Cancer and radiation therapy: current advances and future directions, International Journal of Medical Sciences, 2012;9(3):193–199.5.Wu H, Xie J, Pan Q, Wang B, Hu D, Hu X ,Anticancer agent shikonin is an incompetent inducer of cancer drug resistance, public library of science, 2018;8(1):e52706.6.Choudhari AS, Mandave PC, Deshpande M, Ranjekar P and Prakash,Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice,Frontiers in Pharmacology,2020; 10:1614.7.Newman DJ , Cragg GM ,Natural Products as Sources of New Drugs from 1981 to 2014,Journal ofnatural products, 2016;79(3):629–661.8.Lee WL, Huang JY, Shyur LF. Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms,Oxidativemedicine andCellular Longevity, 2013; 925804, doi: 10.1155/2013/925804.9.Yan X-B, Xie T, Wang SD, Wang Z, Li HY, Ye ZM . Apigenin inhibits proliferation of human chondrosarcoma cells via cell cycle arrest and mitochondrial apoptosis induced by ROS generation-an in vitro and in vivo study, International JournalofClinicalandExperimental Medicine, 2018; 11:1615–1631.10.Lu L, Zhao Z, Liu L, Gong W, Dong J ,Combination of baicalein and docetaxeladditively inhibits the growth of non-small cell lung cancer in vivo , the Traditional medicine Morden medicine, 2018;01:213–218. doi: 10.1142/ S2575900018500131.11. Deng QP, Wang MJ, Zeng X, Chen GG, HuangRY ,Effects of Glycyrrhizin in a Mouse Model ofLung Adeno carcinoma, Cellular PhysiologyandBiochemistry,2017; 41(4) :1383–1392.12. Dou J, Wang Z, Ma L, Peng B, Mao K, Li, C, et al. ,Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence, Oncotarget ,2018; 9(28):20089–20102.13. Adams LS, Phung S, Yee N , Seeram NP, Li L, Chen S ,Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-kinase pathway, Cancer research ,2008; 70(9):3594–3605.14. Zhang W, Su J, Xu H, Yu S, Liu Y, Zhang Y, et al.,Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells , Public library of science, 2017; 12(6) :e0179672.15. Cojocneanu PR, Braicu C, RadulyL, Zanoaga O, Dragos N, Monroig P, et al , Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. Onco. Targets Therapy, 2015; 8:2053–2066.16. Martino E, Casamassima G, Castiglione S, Cellupica E, Pantalone S, Papagni F, et al., Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead, Bioorganic&Medicinal Chemistry Letters,2018; 28(18):2816–2826.17. Kotsakis A, Matikas A, Koinis F, Kentepozidis N, Varthalitis II, KaravassilisV, et al., A multicentre phase II trial of cabazitaxel in patients with advanced non-small-cell lung cancer progressing after docetaxel-based chemotherapy. British journal of cancer,2016; 115(7):784–788.18. Oudard S, Fizazi K, Sengelov L, Daugaard G, Saad F, Hansen S, et al. (2017). Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial-firstana, Internationaljournal of clinical oncology,2017; 35(28):3189–3197.19. Cao B, Chen H, Gao Y, Niu C, Zhang Y, Li L , CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of multidrug-resistant cancer cells in vitro, International JournalofMolecular Medicine, 2015 ; 35(3):771–776.20. Hertzberg RP, Caranfa MJ, Hecht SM, On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme-DNA complex, Biochemistry,1989 ; 28(11) :4629–4638.21. Tozer GM,Kanthou C, Parkins CS, Hill SA, The biology of the combretastatins as tumour vascular targeting agents,International journalofexperimental pathology, 2002; 83:21–38.22. Itokawa H, Wang X, Lee KH,Homoharringtone and related compounds (Boca Raton: CRC Press),2005.23. Skroza N, Bernardini N, Proietti I, PotenzaC ,Clinical utility of ingenol mebutate in the management of actinic keratosis: perspectives from clinical practice, Therapeutics andclinical risk management, 2018; 14:1879–1885.24. Short NJ, Jabbour E, Naqvi K, Patel A, Ning J, Sasaki K, et al., A phase II study of omacetaxine mepesuccinate for patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents, AmericanJournal ofHematology, 2019 ; 94:74–79.25. Paller C J, RudekMA, Zhou XC, Wagner WD, Hudson TS, Anders N, et al., A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: safety, tolerability, and dose determination, Prostate, 2015 ; 75(14):1518–1525.26. Weaver BA, How Taxol/paclitaxel kills cancer cells. Molecular Biologyof theCell, 2014; 25(18):2677–2681.27. Colombo ML,An update on vitamin E, tocopherol and tocotrienol-perspectives, Molecules, 2010; 15(4):2103–2113.
Thrisha et alJournal of Drug Delivery & Therapeutics. 2020; 10(3):293-299ISSN: 2250-1177 [298]CODEN (USA): JDDTAO28. Scorei RI, Popa R Jr,Boron-containing compounds as preventive and chemotherapeutic agents for cancer,Anti-Cancer AgentsinMedicinal Chemistry,2010 ; 10(4) :346–351.29. Granados-Principal S, Quiles JL, Ramirez-Tortosa CL, Sanchez-Rovira P, Ramirez-Tortosa MC ,Hydroxytyrosol: from laboratory investigations to future clinical trials,NutritionReviews ,2010; 68(4):191–206.30. Marques FZ, Markus MA, Morris BJ (2009). Resveratrol: cellular actions of a potent natural chemicalthat confers a diversity of health benefits,TheInternational JournalofBiochemistry&Cell Biology,2009; 41(11):2125–2128.31. Patisaul HB, Jefferson W The pros and cons of phytoestrogens, frontiers neuroendocrinology,2010; 31(4):400–419.32. Kim JW, Amin AR, Shin DM ,Chemoprevention of head and neck cancer with green teapolyphenols,Cancer PreventionResearch, 2010; 3:900–909.33.Huang L , Song Y, Lian J, Wang Z (2017). Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balanceviareducing the activity of phosphoinositide 3-kinase/AKT signaling, Oncology letters,2017;14(1):468–474. 34. Chen H, Zhu B, Zhao L, Liu Y, Zhao F, Feng J, et al., AllicinInhibits Proliferation and Invasion in Vitro and in VivoviaSHP-1-Mediated STAT3 Signaling in Cholangiocarcinoma,Cellular PhysiologyandBiochemistry, 2018;47(2): 641–653. 35. Li J, Zhang C, Jiang H, Cheng J ,Andrographolideinhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth,OncoTargetsandTherapy, 2015; 8:427–435,doi: 10.2147/OTT.S76116.36.Chang JH, Cheng CW, Yang YC, ChenWS, Hung WY, Chow JM, et al., Downregulating CD26/DPPIV by apigenin modulates the interplay between Akt and Snail/Slug signaling to restrain metastasis of lung cancer with multiple EGFR statusesTheJournalofExperimental &Clinical Cancer Research,2018;37(1):199. 37. Tao Y, Zhan S, Wang Y, Zhou G, Liang H, Chen X, et al., (2018). Baicalin, the major component of traditional Chinese medicine Scutellaria baicalensis induces colon cancer cell apoptosis through inhibition of oncomiRNAs,ScientificReports2018; 8:14477,doi: 10.1038/s41598-018-32734-2.38. Kunnumakkara AB, Bordoloi D, Harsha C, Banik K, Gupta SC, Aggarwal BB ,Curcumin mediates anticancer effects by modulating multiple cell signaling pathways,Clinical Science ,2017;131(15):1781–1799. 39. Aras D, Cinar O, Cakar Z, Ozkavukcu S, Can A ,Can dicoumarol be used as a gonad-safe anticancer agent: anin vitroandin vivoexperimental study,Molecular Human Reproduction, 2016;22(1):57–67. 40. ThangapazhamRL, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK ,Green tea polyphenols and its constituent Epigallocatechin gallate inhibits proliferation of human breast cancer cellsin vitroand.In vivo,Cancer Letters,2007;245:232–241. 41. IwanowyczS, Wang J, Hodge J, Wang Y, Yu F, Fan D ,Emodin inhibits breast cancer growth by blocking the tumor-promoting feedforward loop between cancer cells and macrophages,Molecular Cancer Therapeutics, 2016; 15(8):1931–1942. 42. Su X, Jiang X, Meng L, Dong X,Shen Y, Xin Y ,Anticancer activity of sulforaphane: the epigenetic mechanisms and the Nrf2 signaling pathway, OxidativeMedicineandCellular Longevity,2018; 2018:5438179. 43. Hsiao YC, Peng SF, Lai KC, Liao CL, Huang YP, Lin CC, et al., Genistein induces apoptosisin vitroand has antitumor activity against human leukemia HL-60 cancer cell xenograft growthin vivo, Environmental toxicology,2019;34(4):443–456. 44. Joo JH, Hong SS, Cho YR, SeoDW, 10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity, Oncologyreports, 2016;35(2):779–784. 45. Martin A, Fuzer AM, Becceneri AB, da Silva JA, Tomasin R, DenoyerD, et al., [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancerin vivo,Oncotarget,2017; 8(42):72260–72271. 46. Deng QP, Wang MJ, Zeng X, Chen GG, Huang RY(2017). Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma.Cellular PhysiologyandBiochemistry, 2017; 41(4):1383–1392. 47. Gao MQ, Gao H, Han M, Liu KL, Peng JJ, Han YT (2017). Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat,Journal of Cancer Research,2017;7 (7):1501–1514.48. Han M, Gao H, Xie J, Yuan YP, Yuan Q, Gao M Q, et al., Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cellsin vitroandin vivoby activating AMPK signaling pathway,Acta pharmacologica Sinica ,2018;666–676. 49. Subramani R, Gonzalez E, Arumugam A, Nandy S, Gonzalez V, Medel J, et al., Nimbolideinhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition, ScientificReports,2016 ;6: 19819. 50. Feng Y, Yang Y, Fan C, Di S, Hu W, Jiang S, et al.,Pterostilbene Inhibits theGrowth of Human Esophageal Cancer Cells by Regulating Endoplasmic Reticulum Stress, Cellular PhysiologyandBiochemistry, 2016;38(3):1226–1244. 51. Qazi A, Pal J, Maitah M, Fulciniti M, Pelluru D, Nanjappa P, et al., Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma: potential use in chemoprevention and as adjuvant in chemotherapy, translational oncology,2010; 3(6):389–399.52. De La Chapa JJ, Singha PK, Lee DR, Gonzales CB ,Thymol inhibits oral squamous cell carcinoma growthviamitochondria-mediated apoptosis, JournalofOraal PathologyandMedicine ,2018 ; 47(7):674–682. 53.Odeh LH, Talib WH, Basheti IA,Synergistic effect of thymoquinoneand melatonin against breast cancer implanted in mice, Journal of CancerResearchand Therapeutics.,2018; (Supplement):S324–S330.54. Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, et al., Ursolicacid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine,International journal of Clinical Cancer Research,2012;18(18):4942–4953.55. Kuppusamy P, Nagalingam A,Muniraj N, Saxena NK, Sharma D ,Concomitant activation of ETS-like transcription factor-1 and death Receptor-5viaextracellular signal-regulated kinase in withaferin a-mediated inhibition of hepatocarcinogenesis in mice.International JournalofScientific Reports, 2017 ; 7:1794356. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J,Flavonoids as Anticancer Agents. Nutrients,2020; 12(2):457.57. Perez-Vizcaino F, Fraga CG, Research trends in flavonoids and health.ArchivesofBiochemistryandBiophysics, 2018;646:107–112.58. Gorlach S, Fichna J, Lewandowska U,Polyphenols as mitochondria-targeted anticancer drugs ,Cancer Letters , 2015; 366(2):141–149. 59. Kaushik S, Shyam H, AgarwalS, Sharma R, Nag TC, Dwivedi AK, Balapure AK, Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis,Life Scinces,2019;117073.
Thrisha et alJournal of Drug Delivery & Therapeutics. 2020; 10(3):293-299ISSN: 2250-1177 [299]CODEN (USA): JDDTAO60. Jin S, Zhang QY, Kang XM, Wang JX, Zhao WH, Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway.Annals ofOncology,2010; 21(2):263–268.61. Pandey P, Sayyed U, Tiwari RK, Siddiqui MH, Pathak N, Bajpai P , Hesperidin Induces ROS-Mediated Apoptosis along with Cell Cycle Arrest at G2/M Phase in Human Gall Bladder Carcinoma ,Nutrition and cancer,2019;71(4):676–687.62. Palit S, Kar S, Sharma G, Das PK , Hesperetin Induces Apoptosis in Breast Carcinoma by Triggering Accumulation of ROS andActivation of ASK1/JNK Pathway, TheJournalofCellular Physiology,2015 ;230(8) :1729–1739.63. Park S,Lim W, Bazer FW, Song G ,Naringenin suppresses growth of human placental choriocarcinoma via reactive oxygen species-mediated P38 and JNK MAPK pathways. Phytomedicine, 2018;50:238–246.64. Taparia SS, Khanna A, Procyanidin-rich extract of natural cocoa powder causes ROS-mediated caspase-3 dependent apoptosis and reduction of pro-MMP-2 in epithelial ovarian carcinoma cell lines.Biomedicine &pharmacotherapy, 2016;83:130–140. 65. Jeon JS, Kwon S, Ban K, Kwon Hong Y, Ahn C, Sung JS, Choi I ,Regulation of the Intracellular ROS Level Is Critical for the Antiproliferative Eect of Quercetin in the Hepatocellular Carcinoma Cell Line HepG2 ,Nutrition and cancer, 2019 ; 71(5) :861–869.66. Seydi E, Salimi A, Rasekh HR, Mohsenifar Z, Pourahmad, J ,Selective Cytotoxicity of Luteolin and Kaempferol on Cancerous Hepatocytes Obtained from Rat Model of Hepatocellular Carcinoma: Involvement of ROS-Mediated Mitochondrial Targeting,2018;70(4):594–604.67. Tavsan Z, Kayali HA ,Flavonoids showed anticancer effects on the ovarian cancer cells: Involvement of reactive oxygen species, apoptosis, cell cycle and invasion , Biomedicine &pharmacotherapy, 2019;116: 109004.68. Lim W, Ryu S, Bazer FW, Kim SM, Song G ,Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction, TheJournalofCellular Physiology, 2018;233(4):3129–3140
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