Vegetal-Derived Bioactive Compounds as Multidrug Resistance Modulators in Colorectal Cancer
Source abstract
Abstract
Colorectal cancer is one of the leading causes of morbidity and mortality today. Knowledge of its pathogenesis has made it possible to advance the development of different therapeutic strategies. However, the appearance of drug resistance constitutes one of the main causes of treatment failure. Bioactive compounds of vegetable origin are being studied as a new strategy to improve antitumor treatment, due to their ability to regulate the pathways involved in the development of carcinogenesis or processes that are decisive in its evolution, including multidrug resistance. In vitro and in vivo studies of these substances in combination with cytotoxic drugs have shown that they reduce resistance and increase therapeutic efficacy. The objective of this review is to summarize the knowledge that is described in the scientific literature on the antitumor and chemo-sensitizing capacity of vegetable-derived biomolecules such as polyphenols, flavonoids, and terpenes. These compounds may hold a promising future in improving the treatment of colorectal cancer.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Drug-Induced Hepatotoxicity and Protection · Pharmacological Effects of Natural Compounds · Colorectal Cancer Treatments and Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, Spain
Funding
Proyectos I+D+i Junta de Andalucía 2020 · Granada University and ibs. GRANADA · Instituto de Salud Carlos III
References (100+)
Show source-provided references
1. Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., Lim, Y.C., Kaderi Kibria, K.M., Mohiuddin, A.K.M., and Ming, L.C. (2022). Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers, 14.10.3390/cancers14071732 ↗
2. Metastatic Colorectal Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up10.1016/j.annonc.2022.10.003 ↗
3. Systemic Therapy for Colon Cancer10.1016/j.soc.2017.11.001 ↗
4. Colorectal Cancer10.1016/S0140-6736(19)32319-0 ↗
5. Drug Resistance and New Therapies in Colorectal Cancer10.3748/wjg.v24.i34.3834 ↗
6. Irinotecan Combined with Fluorouracil Compared with Fluorouracil Alone. as First-Line Treatment for Metastatic Colorectal Cancer: A Multicentre Randomised Trial10.1016/S0140-6736(00)02034-1 ↗
7. Karthika, C., Sureshkumar, R., Zehravi, M., Akter, R., Ali, F., Ramproshad, S., Mondal, B., Kundu, M.K., Dey, A., and Rahman, M.H. (2022). Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells. Life, 12.10.3390/life12060811 ↗
8. Role of Multidrug Resistance-Associated Proteins in Cancer Therapeutics: Past, Present, and Future Perspectives10.1007/s11356-021-15759-5 ↗
9. The Potential of Plant-Derived Extracts and Compounds to Augment Anticancer Effects of Chemotherapeutic Drugs10.1080/01635581.2022.2069274 ↗
10. Natural Products Derived from Plants as a Source of Drugs10.4103/2231-4040.104709 ↗
11. Najmi, A., Javed, S.A., al Bratty, M., and Alhazmi, H.A. (2022). Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents. Molecules, 27.10.3390/molecules27020349 ↗
12. Polyphenols as Anticancer Agents: Toxicological Concern to Healthy Cells10.1002/ptr.7216 ↗
13. Kubczak, M., Szustka, A., and Rogalińska, M. (2021). Molecular Targets of Natural Compounds with Anti-Cancer Properties. Int. J. Mol. Sci., 22.10.3390/ijms222413659 ↗
14. Guo, Y., Sun, Q., Wu, F.-G., Dai, Y., Chen, X., Guo, Y., Sun, Q., Wu, F., Dai, Y., and Chen Yong Loo, X. (2021). Polyphenol-Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery. Adv. Mater., 33.10.1002/adma.202007356 ↗
15. Engineering Precision Nanoparticles for Drug Delivery10.1038/s41573-020-0090-8 ↗
16. Plant-Derived Bioactive Compounds in Colon Cancer Treatment: An Updated Review10.1016/j.biopha.2022.113384 ↗
17. The Combination of Curcumin and 5-Fluorouracil in Cancer Therapy10.1007/s12272-017-0979-x ↗
18. EGCG Synergizes the Therapeutic Effect of Irinotecan through Enhanced DNA Damage in Human Colorectal Cancer Cells10.1111/jcmm.16718 ↗
19. Effect of Curcumin on Human Colon Cancer Multidrug Resistance in Vitro and in Vivo10.6061/clinics/2013(05)18 ↗
20. Effect of Resveratrol on Drug Resistance in Colon Cancer Chemotherapy10.1039/C8RA08364A ↗
21. Kamran, S., Sinniah, A., Abdulghani, M.A.M., and Alshawsh, M.A. (2022). Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review. Cancers, 14.10.3390/cancers14051100 ↗
22. Costea, T., Vlad, O.C., Miclea, L.C., Ganea, C., Szöllősi, J., and Mocanu, M.M. (2020). Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer. Int. J. Mol. Sci., 21.10.3390/ijms21020401 ↗
23. Flavonoids as an Effective Sensitizer for Anti-Cancer Therapy: Insights into Multi-Faceted Mechanisms and Applicability towards Individualized Patient Profiles10.1007/s13167-021-00242-5 ↗
24. Quercetin Overcomes Colon Cancer Cells Resistance to Chemotherapy by Inhibiting Solute Carrier Family 1, Member 5 Transporter10.1016/j.ejphar.2020.173185 ↗
25. Bukowski, K., Kciuk, M., and Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci., 21.10.3390/ijms21093233 ↗
26. Drug Resistance and Combating Drug Resistance in Cancer
27. Drug Resistance in Cancer: An Overview10.3390/cancers6031769 ↗
28. MDR1/P-Glycoprotein Expression in Colorectal Cancer10.1016/0959-8049(95)00278-Q ↗
29. Targeting CD133 Reverses Drug-Resistance via the AKT/NF-ΚB/MDR1 Pathway in Colorectal Cancer10.1038/s41416-020-0783-0 ↗
30. The Role of MRP1 in the Multidrug Resistance of Colorectal Cancer10.3892/ol.2017.5741 ↗
31. Mechanisms of Drug Resistance in Colon Cancer and Its Therapeutic Strategies10.3748/wjg.v22.i30.6876 ↗
32. Dihydromyricetin Reverses MRP2-Induced Multidrug Resistance by Preventing NF-ΚB-Nrf2 Signaling in Colorectal Cancer Cell10.1016/j.phymed.2020.153414 ↗
33. Drug Resistance in Cancer Therapy and the Role of Epigenetics10.1272/jnms.JNMS.2020_87-508 ↗
34. Das, P.K., Islam, F., and Lam, A.K. (2020). The Roles of Cancer Stem Cells and Therapy Resistance in Colorectal Carcinoma. Cells, 9.10.3390/cells9061392 ↗
35. Neophytou, C.M., Trougakos, I.P., Erin, N., and Papageorgis, P. (2021). Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance. Cancers, 13.10.3390/cancers13174363 ↗
36. Intra-Tumor Heterogeneity from a Cancer Stem Cell Perspective10.1186/s12943-017-0600-4 ↗
37. Cancer Stem Cells (CSCs) in Drug Resistance and Their Therapeutic Implications in Cancer Treatment10.1155/2018/5416923 ↗
38. Tumour Heterogeneity and the Evolution of Polyclonal Drug Resistance10.1016/j.molonc.2014.06.005 ↗
39. Influence of Tumour Micro-Environment Heterogeneity on Therapeutic Response10.1038/nature12626 ↗
40. Natural Products: An Upcoming Therapeutic Approach to Cancer10.1016/j.fct.2019.04.012 ↗
41. Synergistic Effects of Natural Compounds and Conventional Chemotherapeutic Agents: Recent Insights for the Development of Cancer Treatment Strategies10.1016/j.heliyon.2022.e09519 ↗
42. Natural Compounds and Combination Therapy in Colorectal Cancer Treatment10.1016/j.ejmech.2017.12.039 ↗
43. New Insights toward Colorectal Cancer Chemotherapy Using Natural Bioactive Compounds
44. Polyphenols: A Concise Overview on the Chemistry, Occurrence, and Human Health10.1002/ptr.6419 ↗
45. Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer10.3389/fimmu.2019.00729 ↗
46. Bracci, L., Fabbri, A., del Cornò, M., and Conti, L. (2021). Dietary Polyphenols: Promising Adjuvants for Colorectal Cancer Therapies. Cancers, 13.10.3390/cancers13184499 ↗
47. Ko, J.H., Sethi, G., Um, J.Y., Shanmugam, M.K., Arfuso, F., Kumar, A.P., Bishayee, A., and Ahn, K.S. (2017). The Role of Resveratrol in Cancer Therapy. Int. J. Mol. Sci., 18.10.3390/ijms18122589 ↗
48. Resveratrol: An Overview of Its Anti-Cancer Mechanisms10.1016/j.lfs.2018.06.028 ↗
49. Effect of Resveratrol on Proliferation and Telomerase Activity of Human Colon Cancer Cells in Vitro
50. IN-VITRO Evidence for the Protective Properties of the Main Components of the Mediterranean Diet against Colorectal Cancer: A Systematic Review10.1016/j.suronc.2015.08.001 ↗
51. Resveratrol Reverses the Warburg Effect by Targeting the Pyruvate Dehydrogenase Complex in Colon Cancer Cells10.1038/s41598-017-07006-0 ↗
52. Resveratrol Prevents Tumorigenesis in Mouse Model of Kras Activated Sporadic Colorectal Cancer by Suppressing Oncogenic Kras Expression10.1093/carcin/bgu209 ↗
53. Resveratrol and Cancer: Focus on in Vivo Evidence10.1530/ERC-13-0171 ↗
54. Resveratrol Metabolites Inhibit Human Metastatic Colon Cancer Cells Progression and Synergize with Chemotherapeutic Drugs to Induce Cell Death10.1002/mnfr.201200766 ↗
55. Resveratrol Bioavailability and Toxicity in Humans10.1002/mnfr.200900437 ↗
56. Natural Products for Treating Colorectal Cancer: A Mechanistic Review10.1016/j.biopha.2019.109142 ↗
57. Effects of Resveratrol in Combination with 5-Fluorouracil on N-Methylnitrosourea-Induced Colon Cancer in Rats10.1007/s00580-019-02967-2 ↗
58. Buhrmann, C., Yazdi, M., Popper, B., Shayan, P., Goel, A., Aggarwal, B.B., and Shakibaei, M. (2018). Resveratrol Chemosensitizes TNF-β-Induced Survival of 5-FU-Treated Colorectal Cancer Cells. Nutrients, 10.10.3390/nu10070888 ↗
59. Yang, S., Li, W., Sun, H., Wu, B., Ji, F., Sun, T., Chang, H., Shen, P., Wang, Y., and Zhou, D. (2015). Resveratrol Elicits Anti-Colorectal Cancer Effect by Activating MiR-34c-KITLG in Vitro and in Vivo. BMC Cancer, 15.10.1186/s12885-015-1958-6 ↗
60. Resveratrol-Induced Potentiation of the Antitumor Effects of Oxaliplatin Is Accompanied by an Altered Cytokine Profile of Human Monocyte-Derived Macrophages10.1007/s10495-014-0988-x ↗
61. Intensification of Resveratrol Cytotoxicity, pro-Apoptosis, Oxidant Potentials in Human Colorectal Carcinoma HCT-116 Cells Using Zein Nanoparticles10.1038/s41598-022-18557-2 ↗
62. Md, S., Abdullah, S., Alhakamy, N.A., Alharbi, W.S., Ahmad, J., Shaik, R.A., Ansari, M.J., Ibrahim, I.M., and Ali, J. (2021). Development, Optimization, and In Vitro Evaluation of Novel Oral Long-Acting Resveratrol Nanocomposite In-Situ Gelling Film in the Treatment of Colorectal Cancer. Gels, 7.10.3390/gels7040276 ↗
63. Enhanced Antitumor Efficacy of Resveratrol-Loaded Nanocapsules in Colon Cancer Cells: Physicochemical and Biological Characterization
64. Colloidal Mesoporous Silica Nanoparticles Enhance the Biological Activity of Resveratrol10.1016/j.colsurfb.2016.03.076 ↗
65. Enhancing Delivery and Cytotoxicity of Resveratrol through a Dual Nanoencapsulation Approach10.1016/j.jcis.2015.10.022 ↗
66. Montané, X., Kowalczyk, O., Reig-Vano, B., Bajek, A., Roszkowski, K., Tomczyk, R., Pawliszak, W., Giamberini, M., Mocek-Płóciniak, A., and Tylkowski, B. (2020). Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy. Molecules, 25.10.3390/molecules25153342 ↗
67. Curcumin and Colorectal Cancer: An Update and Current Perspective on This Natural Medicine10.1016/j.semcancer.2020.02.011 ↗
68. Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials10.1002/ardp.200900319 ↗
69. Beta-Catenin-Mediated Transactivation and Cell-Cell Adhesion Pathways Are Important in Curcumin (Diferuylmethane)-Induced Growth Arrest and Apoptosis in Colon Cancer Cells10.1038/sj.onc.1205947 ↗
70. Curcumin Effects on Cell Proliferation, Angiogenesis and Metastasis in Colorectal Cancer
71. Pricci, M., Girardi, B., Giorgio, F., Losurdo, G., Ierardi, E., and di Leo, A. (2020). Curcumin and Colorectal Cancer: From Basic to Clinical Evidences. Int. J. Mol. Sci., 21.10.3390/ijms21072364 ↗
72. Cyclooxygenase-2 Expression and Oxidative DNA Adducts in Murine Intestinal Adenomas: Modification by Dietary Curcumin and Implications for Clinical Trials10.1016/j.ejca.2005.10.024 ↗
73. Research Progress on Chemopreventive Effects of Phytochemicals on Colorectal Cancer and Their Mechanisms10.3748/wjg.v22.i31.7058 ↗
74. Curcumin Reverses Oxaliplatin Resistance in Human Colorectal Cancer via Regulation of TGF-β/Smad2/3 Signaling Pathway10.2147/OTT.S199601 ↗
75. Low Curcumin Concentration Enhances the Anticancer Effect of 5-Fluorouracil against Colorectal Cancer10.1016/j.phymed.2021.153547 ↗
76. Hosseini, S.A., Zand, H., and Cheraghpour, M. (2019). The Influence of Curcumin on the Downregulation of MYC, Insulin and IGF-1 Receptors: A Possible Mechanism Underlying the Anti-Growth and Anti-Migration in Chemoresistant Colorectal Cancer Cells. Medicina, 55.10.3390/medicina55040090 ↗
77. Curcumin-Encapsulated Fusion Protein-Based Nanocarrier Demonstrated Highly Efficient Epidermal Growth Factor Receptor-Targeted Treatment of Colorectal Cancer10.1021/acs.jafc.2c04668 ↗
78. Shellac Micelles Loaded with Curcumin Using a PH Cycle to Improve Dispersibility, Bioaccessibility, and Potential for Colon Delivery10.1021/acs.jafc.2c04428 ↗
79. Elbassiouni, F.E., El-Kholy, W.M., Elhabibi, E.-S.M., Albogami, S., and Fayad, E. (2022). Comparative Study between Curcumin and Nanocurcumin Loaded PLGA on Colon Carcinogenesis Induced Mice. Nanomaterials, 12.10.3390/nano12030324 ↗
80. Low, Z.X., Teo, M.Y.M., Nordin, F.J., Dewi, F.R.P., Palanirajan, V.K., and In, L.L.A. (2022). Biophysical Evaluation of Water-Soluble Curcumin Encapsulated in β-Cyclodextrins on Colorectal Cancer Cells. Int. J. Mol. Sci., 23.10.3390/ijms232112866 ↗
81. Redox Responsive Poly(Allylamine)/Eudragit S-100 Nanoparticles for Dual Drug Delivery in Colorectal Cancer10.1016/j.bioadv.2022.213184 ↗
82. Imran, M., Salehi, B., Sharifi-Rad, J., Gondal, T.A., Saeed, F., Imran, A., Shahbaz, M., Fokou, P.V.T., Arshad, M.U., and Khan, H. (2019). Kaempferol: A Key Emphasis to Its Anticancer Potential. Molecules, 24.10.3390/molecules24122277 ↗
83. A Review of the Dietary Flavonoid, Kaempferol on Human Health and Cancer Chemoprevention10.1016/j.foodchem.2012.11.139 ↗
84. Flavonoids and Vitamin E Reduce the Release of the Angiogenic Peptide Vascular Endothelial Growth Factor from Human Tumor Cells10.1093/jn/136.6.1477 ↗
85. Metabolism, Oral Bioavailability and Pharmacokinetics of Chemopreventive Kaempferol in Rats10.1002/bdd.677 ↗
86. Kaempferol Induces Cell Cycle Arrest in HT-29 Human Colon Cancer Cells10.15430/JCP.2013.18.3.257 ↗
87. The Phenolic Compound Kaempferol Overcomes 5-Fluorouracil Resistance in Human Resistant LS174 Colon Cancer Cells10.1038/s41598-018-36808-z ↗
88. Synergistic Effect of Kaempferol and 5-fluorouracil on the Growth of Colorectal Cancer Cells by Regulating the PI3K/Akt Signaling Pathway
89. Kaempferol Sensitizes Cell Proliferation Inhibition in Oxaliplatin-Resistant Colon Cancer Cells10.1007/s12272-021-01358-y ↗
90. Combined Delivery of DOX and Kaempferol Using PEGylated Gold Nanoparticles to Target Colon Cancer10.1007/s10876-020-01961-x ↗
91. Chemistry and Biological Activities of Flavonoids: An Overview10.1155/2013/162750 ↗
92. Pharmacological Basis and New Insights of Quercetin Action in Respect to Its Anti-Cancer Effects10.1016/j.biopha.2019.109604 ↗
93. Reyes-Farias, M., and Carrasco-Pozo, C. (2019). The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int. J. Mol. Sci., 20.10.3390/ijms20133177 ↗
94. Inhibitory Effect of Quercetin on Colorectal Lung Metastasis through Inducing Apoptosis, and Suppression of Metastatic Ability10.1016/j.phymed.2016.09.011 ↗
95. Curcumin and Quercetin Synergistically Inhibit Cancer Cell Proliferation in Multiple Cancer Cells and Modulate Wnt/β-Catenin Signaling and Apoptotic Pathways in A375 Cells10.1016/j.phymed.2018.09.224 ↗
96. Neamtu, A.A., Maghiar, T.A., Alaya, A., Olah, N.K., Turcus, V., Pelea, D., Totolici, B.D., Neamtu, C., Maghiar, A.M., and Mathe, E. (2022). A Comprehensive View on the Quercetin Impact on Colorectal Cancer. Molecules, 27.10.3390/molecules27061873 ↗
97. Lecithin-Stabilized Polymeric Micelles (LsbPMs) for Delivering Quercetin: Pharmacokinetic Studies and Therapeutic Effects of Quercetin Alone and in Combination with Doxorubicin10.1038/s41598-018-36162-0 ↗
98. A Colon-Specific Delivery System for Quercetin with Enhanced Cancer Prevention Based on Co-Axial Electrospinning10.1039/C8FO01216D ↗
99. Almatrood, S.A., Almatroudi, A., Khan, A.A., Alhumaydh, F.A., Alsahl, M.A., and Rahmani, A.H. (2020). Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer. Molecules, 25.10.3390/molecules25143146 ↗
100. le Tea Polyphenol EGCG Inhibited Colorectal-Cancer-Cell Proliferation and Migration via Downregulation of STAT310.1093/gastro/goaa072 ↗