Exploring Mechanisms of Tumorigenesis and Plant-Based Therapies: A Comprehensive Review of Cancer Pathogenesis and Treatment Strategies http://www.doi.org/10.26538/tjnpr/v7i11.2
Article Sidebar
Main Article Content
Abstract
Plant-based compounds have emerged as promising candidates for cancer prevention and treatment due to their ability to modulate metabolizing enzymes, target protein kinases, Matrix metalloproteinases (MMPs), cell cycle progression, Nuclear factor kappa B (NF-κB) signaling, and Cyclooxygenase-2 (COX-2). This review aim to investigate the mechanisms driving tumorigenesis, cancer formation, and to explore the potential of plant-derived compounds in cancer chemotherapy. The study employed a systematic approach in the review of relevant and current literature using online search engines. Plant-based compounds, including flavonoids, polyphenols, and glucosinolates, possess antioxidant properties that reduce DNA damage, induce Phase II enzyme activity, detoxify carcinogens, and inhibit Phase I enzymes. They also regulate protein kinase pathways, inhibit dysregulated lipid kinase signaling, and suppress tumor growth, invasion, metastasis, and angiogenesis. Plant-based therapies targeting NF-κB and COX-2 demonstrate efficacy in suppressing NF-κB activation, modulating gene expression, inhibiting COX-2, and enhancing cancer cell sensitivity to conventional treatments. Plant-derived compounds effectively scavenge free radicals and modulate oxidative stress and cancer-associated signaling pathways. Preclinical studies validate their efficacy in reducing oxidative stress, inhibiting tumor growth, and suppressing metastasis. Recent advancements highlight the importance of genetic alterations, epigenetic modifications, tumor microenvironment, and cancer metabolism in tumorigenesis. Targeted therapies derived from plants, such as curcumin and Epigallocatechin gallate, show promise in targeting specific pathways. Plant-derived compounds also exhibit anti-angiogenic and immune-modulatory properties and can disrupt cancer metabolism. However, comprehensive clinical trials are necessary to evaluate their safety, efficacy, and integration into standard cancer treatment protocols, offering the potential to revolutionize cancer management.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Ahmad A, Ginnebaugh KR, Li Y, Padhye SB, Sarkar FH. Molecular targets of naturopathy in cancer research: bridge to modern medicine. Nutr. 2015; 7(1):321-334.
Rebucci M and Michiels C. Molecular aspects of cancer cell resistance to chemotherapy. Biochem Pharmacol. 2013; 85(9):1219-1226.
VanderVorst K, Hatakeyama J, Berg A, Lee H, Carraway III, KL. Cellular and molecular mechanisms underlying planar cell polarity pathway contributions to cancer malignancy. In Sem Cell Dev Biol. 2018; 81:78-87.
Guo YJ, Pan WW, Liu SB, Shen ZF, Xu Y, Hu LL. ERK/MAPK signaling pathway and tumorigenesis. Exp Ther Med. 2020; 19(3):1997-2007.
García-Gómez R, Bustelo XR, Crespo P. Protein to protein interactions: Emerging on targets in the RAS-ERK pathway. Trends Cancer. 2018; 4(9):616-633.
Zhao GS, Gao ZR, Zhang Q, Tang XF, Lv YF, Zhang ZS, Guo QN. TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma and predicts a favorable prognosis. J Exp Clin Cancer Res. 2018; 37:1-17.
Ou A, Ott M, Fang D, Heimberger AB. The role and therapeutic targeting of JAK/STAT signaling in glioblastoma. Cancers 2021; 13(3):437.
Mariaule G and Belmont P. Cyclin-dependent kinase inhibitors as marketed anticancer drugs: where are we now? A short survey. Mol. 2014; 19(9):14366-14382.
Azad T, Nouri K, Janse van Rensburg HJ, Maritan SM, Wu L, Hao Y, Yang X. A gain-of-functional screen identifies the Hippo pathway as a central mediator of receptor tyrosine kinases during tumorigenesis. Oncol. 2020 39(2):334-355.
Matozaki T, Kotani T, Murata Y, Saito Y. Roles of Src family kinase, Ras, and mTOR signaling in intestinal epithelial homeostasis and tumorigenesis. Cancer Sci. 2021; 112(1):16-21.
Vallejo MJ, Salazar L, Grijalva M. Oxidative stress modulation and ROS-mediated toxicity in cancer: a review on in vitro models for plant-derived compounds. Oxid Med Cellul Longev. 2017; 2017: Article ID 4586068, 9 pages
Esmeeta A, Adhikari S, Dharshnaa V, Swarnamughi P, Maqsummiya ZU, Banerjee A, Duttaroy AK. Plant-derived bioactive compounds in colon cancer treatment: An updated review. Biomed Pharmacother. 2022; 153:113384.
Dehelean CA, Marcovici I, Soica C, Mioc M, Coricovac D, Iurciuc S, Pinzaru I. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Mol. 2021; 26(4):1109.
Ryland LK, Fox TE, Liu X, Loughran TP, Kester M. Dysregulation of sphingolipid metabolism in cancer. Cancer Biol Ther. 2011; 11(2):138-149.
Memmott RM and Dennis PA. The role of the Akt/mTOR pathway in tobacco carcinogen-induced lung tumorigenesis. Clin Cancer Res. 2010; 16(1):4-10.
Davis WJ, Lehmann PZ, Li W. Nuclear PI3K signaling in cell growth and tumorigenesis. Front Cell Dev Biol. 2015;
Peifer C and Alessi DR. Small‐molecule inhibitors of PDK1. Chem Med Chem: Chem Enab Drug Discov. 2008; 3(12):1810-1838.
Samadi N, Bekele R, Capatos D, Venkatraman G, Sariahmetoglu M, Brindley DN. Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases concerning tumor progression, angiogenesis, metastasis, and chemo-resistance. Biochim. 2011; 93(1):61-70.
Kang DW and Choi KY. Functional regulation of phospholipase D expression in cancer and inflammation. J Biol Chem. 2014; 289(33):22575-22582.
Yao Y, Wang X, Li H, Fan J, Qian X, Li H, Xu Y. Phospholipase D is a key modulator of cancer progression. Biol Rev. 2020; 95(4):911-935.
Dei Cas M and Ghidoni R. Cancer prevention and therapy with polyphenols: Sphingolipid-mediated mechanisms. Nutr. 2018; 10(7):940.
Sridevi V, Naveen P, Karnam VS, Reddy PR, Arifullah M. Beneficiary and adverse effects of phytoestrogens: A potential constituent of a plant-based diet. Curr Pharm Desig. 2021; 27(6):802-815.
Park MH. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun. 2011; 412(4):710-715.
Shafei A, Ramzy MM, Hegazy AI, Husseny AK, El-Hadary UG, Taha MM, Mosa AA. The molecular mechanisms of action of the endocrine-disrupting chemical bisphenol A in the development of cancer. Gene. 2018; 647:235-243.
Brooke GN and Bevan CL. The role of androgen receptor mutations in prostate cancer progression. Curr Genom. 2009; 10(1):18-25.
Takayama KI and Inoue S. Transcriptional network of androgen receptor in prostate cancer progression. Int J Urol. 2013; 20(8):756-768.
Chhabra Y, Waters MJ, Brooks AJ. Role of the growth hormone–IGF-1 axis in cancer. Expert Rev Endocrinol Metab. 2011; 6(1):71-84.
Karagiannis AK, Philippou A, Tseleni-Balafouta S, Zevolis E, Nakouti T, Tsopanomichalou-Gklotsou M, Koutsilieris M. IGF-IEc expression is associated with advanced differentiated thyroid cancer. Anticancer Res. 2019; 39(6):2811-2819.
Ramírez-de-Arellano A, Villegas-Pineda JC, Hernández-Silva CD, Pereira-Suárez AL. The relevant participation of prolactin in the genesis and progression of gynecological cancers. Front Endocrinol. 2021; 12:747810
Student S, Hejmo T, Poterała-Hejmo A, Leśniak A, Bułdak R. Anti-androgen hormonal therapy for cancer and other diseases. Eur J Pharmacol. 2020; 866:172783.
Zhang J, Sun J, Bakht S, Hassan W. (2022). Recent Development and Future Prospects of Molecular Targeted Therapy in Prostate Cancer. Curr Mol Pharmacol. 15(1):159-169.
Papoutsi Z, Kassi E, Mitakou S, Aligiannis N, Tsiapara A, Chrousos GP, Moutsatsou P. Acteoside and martensite exhibit estrogenic/antiestrogenic properties. The J Steroid Biochem Mol Biol. 2006; 98(1):63-71.
Landete JM, Arqués J, Medina M, Gaya P, de Las Rivas B, Muñoz, R. Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr. 2016; 56(11):1826-1843.
Kai L and Levenson AS. The combination of resveratrol and antiandrogen flutamide has a synergistic effect on androgen receptor inhibition in prostate cancer cells. Anticancer Res. 2011; 31(10):3323-3330.
Chakraborty S, Kumar A, Butt NA, Zhang L, Williams R, Rimando AM, Levenson AS. Molecular insight into the differential anti-androgenic activity of resveratrol and its natural analogs: in silico approach to understanding biological actions. Mol BioSyst. 2016; 12(5):1702-1709.
Wang JL, Gold KA, Lippman SM. Natural-agent mechanisms and early-phase clinical development. Nat Prod Cancer Prev Ther. 2013; 329:241-252.
Montané X, Kowalczyk O, Reig-Vano B, Bajek A, Roszkowski K, Tomczyk R, Tylkowski B. Current perspectives of the applications of polyphenols and flavonoids in cancer therapy. Mol. 2020; 25(15):3342.
Bonnans C, Chou J, Werb Z. Remodeling the extracellular matrix in development and disease. Nat Rev Mol Cell Boil. 2014; 15(12):786-801.
Niland S, Riscanevo AX, Eble J. A. Matrix metalloproteinases shape the tumor microenvironment in cancer progression. Int J Mol Sci. 2022; 23(1):146.
Cheng YT, Yang CC, Shyur LF. Phytomedicine—Modulating oxidative stress and the tumor microenvironment for cancer therapy. Pharmacol Res. 2016; 114:128-143.
Anuar NN, Zulkafali NIN, Ugusman A. Modulation of matrix metalloproteinases by plant-derived products. Curr Cancer Drug Targ. 2021; 21(2):91-106.
Dang F, Nie L, Wei W. Ubiquitin signaling in cell cycle control and tumorigenesis. Cell Death Differ. 2021; 28(2):427-438.
Guo H, Deng H, Liu H, Jian Z, Cui H, Fang J, Zhao L. Nickel carcinogenesis mechanism: cell cycle dysregulation. Environ Sci Pollut Res. 2021; 28:4893-4901.
Ubhenin A, Uwakwe A, Falodun A, Engel-Lutz N, Onwuka F, Langer P. Anti-proliferative and Pro-apoptotic Effects of Caesalpinia bonduc Extract and its Fractions in Estrogen-Sensitive Human Breast Adenocarcinoma Cell Line. J Herbs, Spices Med Plants. 2013; 19(2):159-167.
Çoban EA, Tecimel D, Şahin F, Deniz AAH. Targeting cancer metabolism and cell cycle by plant-derived compounds. Adv Exp Med Biol. 2020; 1247:125-134.
Nguyen LT, Lee YH, Sharma AR, Park JB, Jagga S, Sharma G, Nam JS. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity. The Korean J Physiol Pharmacol. 2017; 21(2):205.
George BP and Abrahamse H. A review on novel breast cancer therapies: Photodynamic therapy and plant-derived agent-induced cell death mechanisms. Anti-Cancer Agents in Med Chem (Formerly Curr Med Chem-Anti-Cancer Agents), 2016; 16(7):793-801.
Androutsopoulos VP, Tsatsakis AM, Spandidos DA. Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer. 2009; 9:1-17.
Talalay P and Fahey JW. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. The J Nutr. 2001; 131(11):3027S-3033S
Pathania S, Bhatia R, Baldi A, Singh R, Rawal RK. Drug metabolizing enzymes and their inhibitors' role in cancer resistance. Biomed Pharmacother. 2018; 105:53-65.
Kaur G, Gupta SK, Singh P, Ali V, Kumar V, Verma M. Drug-metabolizing enzymes: role in drug resistance in cancer. Clin Transl Oncol. 2020; 22:1667-1680.
Giudice A and Montella M. Activation of the Nrf2–ARE signaling pathway: a promising strategy in cancer prevention. Bioessays. 2006; 28(2):169-181.
Stading R, Chu C, Couroucli X, Lingappan K, Moorthy B. Molecular role of cytochrome P4501A enzymes in oxidative stress. Curr Opin Toxicol. 2020; 20:77-84.
Standing R, Gastelum G, Chu C, Jiang W, Moorthy B. Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer. In Sem Cancer Biol. 2021; 76:3-16.
Singh RP, Padmavathi B, Rao AR. Modulatory influence of Adhatoda vesica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism, antioxidant status, and lipid peroxidation in mice. Mol Cell Biochem. 2000; 213:99-109.
Garg R, Gupta S, Maru GB. Dietary curcumin modulates transcriptional regulators of phase I and phase II enzymes in benzo [a] pyrene-treated mice: mechanism of its anti-initiating action. Carcinog. 2008; 29(5):1022-1032.
Baldwin AS. Regulation of cell death and autophagy by IKK and NF‐κB: critical mechanisms in immune function and cancer. Immunol Rev 2012; 246(1):327-345.
Barroso-González J, Auclair S, Luan S, Thomas L, Atkins KM, Aslan JE, Thomas LL, Zhao J, Zhao Y, Thomas G. "PACS-2 mediates the ATM and NF-κB-dependent induction of anti-apoptotic Bcl-xL in response to DNA damage. Cell Death Differ. 2016; 23(9):1448-1457.
Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, Hong Y. Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of the cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 2015; 357(2):520-526.
Chaithongyot S, Jantaree P, Sokolova O, Naumann M. NF-κB in gastric cancer development and therapy. Biomed. 2021; 9(8):870.
Mortezaee K, Najafi M, Farhood B, Ahmadi A, Shabeeb D, Musa AE. NF‐κB targeting for overcoming tumor resistance and normal tissue toxicity. J Cell Physiol. 2019; 234(10):17187-17204. 3:24.
Cohen BL, Gomez P, Omori Y, Duncan RC, Civantos F, Soloway MS, Lokeshwar BL. Cyclooxygenase‐2 (COX‐2) expression is an independent predictor of prostate cancer recurrence. Int J Cancer, 2006; 119(5):1082-1087.
Li S, Jiang M, Wang L, Yu S. Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. Biomed Pharmacother. 2020; 129:110389.
Peng G, Dixon DA, Muga SJ, Smith TJ, Wargovich MJ. Green tea polyphenol (−)‐epigallocatechin‐3‐gallate inhibits cyclooxygenase‐2 expression in colon carcinogenesis. Mol Carcinog. 2006; 45(5):309-319.
Amirova KM, Dimitrova P, Marchev AS, Aneva IY, Georgiev MI. Clinopodium vulgare L.(wild basil) extract and its active constituents modulate cyclooxygenase-2 expression in neutrophils. Food Chem Toxicol. 2019; 124:1-9.
Kruk J and Aboul-Enein HY. Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem. 2017; 17(11):904-919.
Klaunig JE. Oxidative stress and cancer. Curr Pharm Desig. 2018; 24(40):4771-4778.
Azmanova M and Pitto‐Barry A. Oxidative stress in cancer therapy: friend or enemy? Chem Biochem. 2022; 23(10):e202100641
Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, Singhal SS. Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment. Cancer Lett. 2018; 413:122-134.
Chatterjee M and Sengupta S. Emerging roles of long non-coding RNAs in cancer. J Biosci. 2019; 44:1-14.
Le P, Romano G, Nana-Sinkam P, Acunzo M. Non-Coding RNAs in cancer diagnosis and therapy: Focus on lung cancer. Cancers. 2021; 13(6):1372.
Ilango S, Paital B, Jayachandran P, Padma PR, Nirmaladevi R. Epigenetic alterations in cancer. Front Biosci-Landmark. 2020; 25(6):1058-1109.
Huo M, Zhang J, Huang W, Wang Y. The interplay among metabolism, epigenetic modifications, and gene expression in cancer. Front Cell Dev Biol. 2021; 9:793428.
Arneth B. Tumor microenvironment. Medicine, 2019; 56(1):15.
Anderson NM and Simon MC. The tumor microenvironment. Curr Biol. 2020; 30(16):R921-R925.
Hirschey MD, DeBerardinis RJ, Diehl AME, Drew JE, Frezza C, Green MF, Team TV. Dysregulated metabolism contributes to oncogenesis. In Seminars in cancer boil. 2015; 35:S129-S150).
Marusyk A, Janiszewska M, Polyak K. Intratumor heterogeneity: the rosetta stone of therapy resistance. Cancer Cell. 2020; 37(4):471-484.
Koury J, Lucero M, Cato C, Chang L, Geiger J, Henry D, Tran A. Immunotherapies: exploiting the immune system for cancer treatment. J Immunol Res. 2018; 2018:9585614.
Hirschey MD, DeBerardinis RJ, Diehl AME, Drew JE, Frezza C, Green MF, Team TV. Dysregulated metabolism contributes to oncogenesis. In Sem Cancer Biol. 2015; 35:S129-S150).
Kim SH and Baek KH. Regulation of cancer metabolism by deubiquitinating enzymes: The Warburg effect. Int J Mol Sci. 2021; 22(12):6173.
Herisman MW, Gani AP, Murwanti R. Effect of Curcuma mangga and Curcuma longa on Oxidative Stress-related Diseases and ROS Level: A Recent Study. Trop J Nat Prod Res. 2022; 6(5):668-672.