* Corresponding Author
The Synergistic Effect of Combination of Pentagamavunone-1 with Diosmin, Galangin, and Piperine in WiDr Colon Cancer Cells: In vitro and Target Protein Prediction
https://doi.org/10.22146/jtbb.80975 Muthi Ikawati(1*), Hajidah Musyayyadah(2), Yurananda Magnalia Putri(3), Ummi Maryam Zulfin(4), Febri Wulandari(5), Dyaningtyas Dewi Pamungkas Putri(6), Edy Meiyanto(7)
(1) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(2) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(3) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(4) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(5) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(6) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia; Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(7) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(*) Corresponding Author
Abstract
Pentagamavunone-1 (PGV-1) is a curcumin analog with a prominent anti-cancer potency in vitro and in vivo for several cancer types, including colon cancer. Combining PGV-1 with natural compounds such as diosmin, galangin, and piperine can enhance its effectiveness due to their promising chemoprevention properties. We aimed to evaluate the effectiveness of combining PGV-1 with diosmin, galangin, or piperine for colon cancer by using in vitro and bioinformatic approaches to predict their target proteins. WiDr cells were used as a model for colon adenocarcinoma (COAD). The cell viability under a single or combination treatment of PGV-1 and diosmin, galangin, or piperine was evaluated using direct counting by the trypan blue exclusion test. SwissTargetProtein, UALCAN, and OncoLnc were utilized to predict target proteins of the compounds in COAD, the expression level of target proteins in COAD, and the survival rate of patients with overexpressed target proteins, respectively. The IC50 values for PGV-1, diosmin, galangin, and piperine were 2.8´10-2 µg/mL, 81 µg/mL, 7 µg/mL, and 172 µg/mL, respectively. All the tested natural compounds showed synergistic effects when combined with PGV-1 at low concentrations. Eleven proteins that were overexpressed in COAD were identified as potential targets. Overlapped predicted targets of PGV-1 and galangin or piperine were CDK1, MET, and TOP2A. The high expression of another set of predicted target proteins, SCD, CA9, and SQLE, led to lower survival rates in COAD patients. We concluded that combinations of PGV-1 with natural compounds can synergistically enhane its anti-cancer activity for colon cancer.
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Allemani, C. et al., 2018. Global Surveillance of Trends in Cancer Survival 2000-14 (CONCORD-3): Analysis of Individual Records for 37513025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries. Lancet, 391(10125), pp.1023-1075. doi: 10.1016/S0140-6736(17)33326-3
Anaya, J., 2016. OncoLnc: Linking TCGA Survival Data to mRNAs, miRNAs, and lncRNAs. PeerJ Computer Science, 2, e67. doi: 10.7717/peerj-cs.67
Argiles, G. et al., 2020. Localised Colon Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Annals of Oncology, 31(10), pp.1291-1305. doi: 10.1016/j.annonc.2020.06.022
Aslanturk, O.S., 2017. In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages. In Genotoxicity - A Predictable Risk to Our Actual World. London: IntechOpen. doi: 10.5772/intechopen.71923
Avand, A., Akbari, V., & Shafizadegan, S., 2018. In Vitro Cytotoxic Activity of a Lactococcus lactis Antimicrobial Peptide Against Breast Cancer Cells. Iranian Journal Biotechnology, 16(3), pp.213-220. doi: 10.21859/ijb.1867
Chandrashekar, D.S. et al., 2017. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8), pp.649-658. doi: 10.1016/j.neo.2017.05.002
Chen, Q. et al., 2020. Profiling of Flavonoid and Antioxidant Activity of Fruit Tissues from 27 Chinese Local Citrus Cultivars. Plants, 9(2), e196. doi: 10.3390/plants9020196
Chen, T.R. et al., 1987. WiDr is a Derivative of Another Colon Adenocarcinoma Cell Line, HT-29. Cancer Genetic, 27(1), pp.125-134. doi: 10.1016/0165-4608(87)90267-6
Daina, A. et al., 2019. SwissTargetPrediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules. Nucleic Acids Research, 47(W1), pp.W357-W364. doi: 10.1093/nar/gkz382
Endah et al., 2021. Piperine Increases Pentagamavunone-1 Anti-cancer Activity on 4T1 Breast Cancer through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins. Iranian Journal of Pharmaceutical Research, 21(1), e123820. doi: 10.5812/ijpr.123820
Hasbiyani, N.A.F. et al., 2021. Bioinformatics Analysis Confirms the Target Protein Underlying Mitotic Catastrophe of 4T1 Cells Under Combinatorial Treatment of PGV-1 and Galangin. Scientia Pharmaceutica, 89(3), e38, doi: 10.3390/scipharm89030038
Heberle, H. et al., 2015. InteractiVenn: A Web-Based Tool for The Analysis of Sets Through Venn Diagrams. BMC Bioinformatics, 16, e169. doi: 10.1186/s12859-015-0611-3
Huang, H, et al., 2020. Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells. Molecules, 25(7), e1579. doi: 10.3390/molecules25071579
Ikawati, M. & Septisetyani, E.P., 2018. Pentagamavunone-0 (PGV-0), A Curcumin Analog, Enhances Cytotoxicity of 5-Fluorouracil and Modulates Cell Cycle in WiDr Colon Cancer Cells. Indonesian Journal of Cancer Chemoprevention, 9(1), pp.23-31. doi: 10.14499/indonesianjcanchemoprev9iss1pp23-31
Kusuma, S.M.W. et al., 2022. Molecular Mechanism of Inhibition of Cell Proliferation: An in Silico Study of The Active Compounds in Curcuma longa as An Anticancer. Journal of Tropical Biodiversity and Biotechnology, l7(3), jtbb74905. doi: 10.22146/jtbb.74905
Lestari, B. et al., 2019. Pentagamavunon-1 (PGV-1) Inhibits ROS Metabolic Enzymes and Suppresses Tumor Cell Growth by Inducing M Phase (Prometaphase) Arrest and Cell Senescence. Scientific Reports, 9(1), 14867. doi: 10.1038/s41598-019-51244-3
Manayi, A. et al., 2018. Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies. Current Medicinal Chemistry, 25(37), pp.4918-4928. doi: 10.2174/0929867324666170523120656
Meiyanto, E. et al., 2014. Curcumin and Its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation. Asian Pacific Journal of Cancer Prevention, 15(1), pp.179-184. doi: 10.7314/apjcp.2014.15.1.179
Meiyanto, E. et al., 2018. Curcumin Analog Pentagamavunon-1 (PGV-1) Sensitizes WiDr Cells to 5-Fluorouracil through Inhibition of NF-κB Activation. Asian Pacific Journal of Cancer Prevention, 19(1), pp.49-56. doi: 10.22034/APJCP.2018.19.1.49
Meiyanto, E. et al., 2019. Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation. Advanced Pharmaceutical Bulletin, 9(3), pp.445-452. doi: 10.15171/apb.2019.053
Meiyanto, E. et al., 2021. The Target Differences of Anti-Tumorigenesis Potential of Curcumin and its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells. Advanced Pharmaceutical Bulletin, 11(1), pp. 88-196. doi: 10.34172/apb.2021.020
Musyayyadah, H. et al., 2021. The Growth Suppression Activity of Diosmin and PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins. Asian Pacific Journal of Cancer Prevention, 22(9), pp.2929-2938. doi: 10.31557/APJCP.2021.22.9.2929
Niyibizi, J.B. et al., 2020. Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds. Journal of Tropical Medicine, 2020, 1643015. doi: 10.1155/2020/1643015
Rejhova, A. et al., 2018. Natural compounds and combination therapy in colorectal cancer treatment. European Journal of Medicinal Chemistry, 144, pp.582-594. doi: 10.1016/j.ejmech.2017.12.039
Russo, R. et al., 2018. Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers. Molecules, 23(9), e2174. doi: 10.3390/molecules23092174
Siegel, R.L. et al., 2021. Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians, 71(1), pp.7-33. doi: 10.3322/caac.21654
Stoffel, E.M. & Murphy, C.C., 2020. Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology, 158(2), pp.341-353. doi: 10.1053/j.gastro.2019.07.055
Strober, W., 2015. Trypan Blue Exclusion Test of Cell Viability. Current Protocols in Immunology, 111(1), pp.A3.B.1-A3.B.3. doi: 10.1002/0471142735.ima03bs111
Sung, H. et al., 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), pp.209-249. doi: 10.3322/caac.21660
Utomo, R.Y. et al., 2020. The Chemopreventive Potential of Diosmin and Hesperidin for COVID-19 and Its Comorbid Diseases. Indonesian Journal of Cancer Chemopreventio, 11(3), pp.154-167. doi: 10.14499/indonesianjcanchemoprev11iss3pp154-167
Wulandari, F. et al., 2021. Curcumin Analogs, PGV-1 and CCA-1.1 Exhibit Anti-migratory Effects and Suppress MMP9 Expression on WiDr Cells. Indonesian Biomedical Journal, 13(3), pp.271-280. doi: 10.18585/inabj.v13i3.1583
Zheng, Y. et al., 2020. Metabolism and Pharmacological Activities of The Natural Health-Benefiting Compound Diosmin. Food & Function, 21(10), pp.8472-8492. doi: 10.1039/d0fo01598a
DOI: https://doi.org/10.22146/jtbb.80975
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