Peperomia pellucida Extract Enhances the Cytotoxicity of Doxorubicin against 4T1 Breast Cancer Cells
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Abstract
The use of natural agents in co-chemotherapy to enhance activity while minimizing adverse effect has been greatly explored. Doxorubicin, one of the chemotherapeutic drugs for breast cancer, exhibits serious adverse effects on the normal cells. Peperomia pellucida has potential as an anticancer and antioxidant agent. The present study aimed to investigate the combined effect of Peperomia pellucida extract (PPE) and doxorubicin on triple-negative breast cancer (TNBC) cells (4T1). PPE was obtained by maceration in 96% ethanol. The cytotoxic activity was determined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. PPE exhibited moderate cytotoxic effect against 4T1 cells with IC50 value of 83.86 µg/mL. PPE showed synergistic activity when combined with doxorubicin (IC50 = 0.4 µg/mL) and was less toxic to Vero cell lines (IC50 = 145.36 µg/mL). The findings from this study provide credence to the idea of using PPE in conjunction with doxorubicin as a chemotherapeutic agent to treat TNBC.
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References
1. Wakharde AA, Awad AH, Bhagat A, Karuppayil SM. Synergistic Activation of Doxorubicin Against Cancer: A Review. Am J Clin Microbiol Antimicrob. 2018; 1(2):1-6.
2. Hu X and Zhang H. Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and is Inhibited by Epithelial-Mesenchymal
Transition (EMT). Med Sci Monit. 2019; 25:3617–3623.
3. Syahputra RA, Harahap U, Dalimunthe A, Pandapotan M, Satria D. Protective effect of Vernonia amygdalina Delile Against Doxorubicin-Induced Cardiotoxicity. Heliyon. 2021; 7(7):e07434.
4. Ahlina FN, Nugraheni N, Salsabila IA, Haryanti S, Da’i M, Meiyanto E. Revealing the Reversal Effect of Galangal (Alpinia galanga L.) Extract Against Oxidative Stress in Metastatic Breast Cancer Cells and Normal Fibroblast Cells Intended as a Co- Chemotherapeutic and Anti-Ageing Agent. Asian Pac J Cancer Prev. 2020; 21(1):107–117.
5. Huang M, Lu JJ, Ding J. Natural Products in Cancer Therapy: Past, Present and Future. Nat Prod Bioprospect. 2021; 11(1):5–13.
6. Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Natural Products in Drug Discovery: Advances and Opportunities. Nat Rev Drug Discov. 2021; 20(3):200–216.
7. Zulfin UM, Rahman A, Hanifa M, Utomo RY, Haryanti S, Meiyanto E. Reactive Oxygen Species and Senescence Modulatory Effects of Rice Bran Extract on 4T1 and NIH-3T3 Cells Co-Treatment with Doxorubicin. Asian Pac J Trop Biomed. 2021; 11(4):9174-9182.
8. Ahmad I, Hikmawan BD, Mun’im A, Sulistiarini R. Peperomia pellucida (L.) Kunth Herbs: A Comprehensive Review on Phytochemical, Pharmacological, Extraction Engineering Development, and Economic Promising Perspectives. J Appl Pharm Sci. 2023; 13(01):001–009.
9. Lydia T, Nareshwaran G, Ahmad Faris MA, Rosna Mat T. The Comparative Antimicrobial and Anticancer of Chemical Extract from In Vitro and In Vivo Peperomia pellucida Plantlet. J Appl Biol Biotechnol. 2021; 9(2):115-123.
10. Hartati S, Angelina M, Dewiyanti I, Meilawati L. Isolation and Characterization Compounds from Hexane and Ethyl Acetate Fractions of Peperomia pellucida L. J Trop Life Sci. 2015; 5(3):117–122.
11. Okoh S, Iweriebor B, Okoh O, Okoh A. Bioactive Constituents, Radical Scavenging, and Antibacterial Properties of The Leaves and Stem Essential Oils from Peperomia pellucida (L.) Kunth. Phcog Mag. 2017; 13(51):392-400-.
12. Narayanamoorthi V, Vasantha K, Rency RC, Maruthasalam A. GC MS determination of Bioactive Components of Peperomia pellucida (L.) Kunth. Biosci Discov. 2015; 6(2):83-88.
13. Alves NSF, Kaory Inoue SG, Carneiro AR, Albino UB, Setzer WN, Maia JG, Andrade EH, da Silva JKR. Variation in Peperomia pellucida Growth and Secondary Metabolism after Rhizobacteria Inoculation. PLOS ONE. 2022; 17(1):e0262794.
14. Parwati P and Wikantyasning RE. Optimization of Cream Formulation Containing Leaf Extract and Chitosan Nanoparticles. Trop J Nat Prod Res. 2023; 7(11):5183-5187.
15. Pappachen LK and Chacko A. Preliminary Phytochemical Screening and In-Vitro Cytotoxicity Activity of Peperomia pellucida Linn. Pharmacie Globale. 2013; 4(8):1-5.
16. Yadav R and Agarwala M. Phytochemical Analysis of Some Medicinal Plants. J Phytol. 2011; 3(2):10-14.
17. Musyayyadah H, Wulandari F, Nangimi AF, Anggraeni A, Ikawati M, Meiyanto E. The Growth Suppression Activity of Diosmin and
PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins. Asian Pac J Cancer Prev. 2021; 22(9):2929–2938.
18. Susanto H, Widodo N, Masruri M, Ulfa SM, Fitriana N, Rollando R. The Cytotoxic Effects, Stimulation of p53, Caspase 3, and Bax by Potent Fractions Derived from the Leptastrea purpurea Sponge. Trop J Nat Prod Res. 2024; 8(6):7459–7465.
19. Da’i M, Meilinasary KA, Suhendi A, Haryanti S. Selectivity Index of Alpinia galanga Extract and 1’-Acetoxychavicol Acetate on Cancer Cell Lines. Indones J Cancer Chemoprev. 2019; 10(2):95-100.
20. Wulandari F, Ikawati M, Novitasari D, Kirihata M, Kato J ya, Meiyanto E. New Curcumin Analog, CCA-1.1, Synergistically Improves the Antiproliferative Effect of Doxorubicin Against T47D Breast Cancer Cells. Indones J Pharm. 2020; 31(4):244–256.
21. Anuchapreeda S, Anzawa R, Viriyaadhammaa N, Neimkhum W, Chaiyana W, Okonogi S, Usuki T. Isolation and Biological Activity of Agrostophillinol from Kaffir Lime (Citrus hystrix) Leaves. Bioorg Med Chem Lett. 2020; 30(14):127256 127260.
22. Tunjung WAS, Fajarina S, Prabowo BH, Damayanti F, Widyasari A, Sasongko AB, Indrianto A, Semiarti E, Hidayati L. Evaluation of Anticancer Bioactive Compounds and Cytotoxicity of Citrus hystrix Dc. Callus Extract Post Preservation. Indones J Pharm. 2021; 32(2):179 - 192.
23. Meiyanto E, Husnaa U, Kastian RF, Putri H, Larasati1 YA, Khumaira A, Pamungkas DDP, Jenie RI, Kawaichi M, Lestari B, Yokoyama T. Kato J. The Target Differences of Anti-Tumorigenesis Potential of Curcumin and Its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells. Adv Pharm Bull. 2021; 11(1):188 - 196.
24. Suhendi A, Wikantyasning ER, Setyadi G, Wahyuni AS, Da’i M. Acetoxy Chavicol Acetate (ACA) Concentration and Cytotoxic Activity of Alpinia galanga Extract on HeLa, MCF7 and T47D Cancer Cell Lines. Indones J Cancer Chemoprev. 2017; 8(2):81-90.
25. Haryanti S, Zulfin U, Salsabila I, Wulandari F, Meiyanto E. The Cytotoxic and Anti-Migratory Properties of Caesalpinia sappan and Ficus septica, in Combination with Doxorubicin on 4T1 TNBC Cells with Nephroprotective Potential. Asian Pac J Cancer Prev. 2022; 23(2):743–752.
26. DiMarco-Crook C, Rakariyatham K, Li Z, Du Z, Zheng J, Wu X, Xiao H. Synergistic Anticancer Effects of Curcumin and 3’,4’-Didemethylnobiletin in Combination on Colon Cancer Cells. J Food Sci. 2020; 85(4):1292–1301.
27. Amalina ND, Salsabila IA, Zulfin UM, Jenie RI, Meiyanto E. In Vitro Synergistic Effect of Hesperidin and Doxorubicin Downregulates Epithelial-Mesenchymal Transition in Highly Metastatic Breast Cancer Cells. J Egypt Natl Cancer Inst. 2023; 35(6):1-13.
28. Edityaningrum CA, Khairurrizki A, Nurani LH, Bachri MS, Yuliani S, Utami D, Kintoko, Nurkhasanah, Irham LM, Zakaria ZA. Co-Chemotherapy Effect of The Extract of Hibiscus Sabdariffa and Cisplatin Against Apoptosis and Anti-Proliferation on T47d and Vero Cells. Trop J Nat Prod Res. 2024; 8(6):7509–7513.
29. Amalina N, Nurhayati IP, Meiyanto E. Doxorubicin Induces Lamellipodia Formation and Cell Migration. Indones J Cancer Chemoprev. 2017; 8(2):61-66.
30. Wulandari F, Ikawati M, Kirihata M, Kato JY, Meiyanto E. Curcumin Analogs, PGV-1 and CCA-1.1 Exhibit Anti-migratory Effects and Suppress MMP9 Expression on WiDr Cells. Indones Biomed J. 2021; 13(3):271–280.
31. Ikawati M, Jenie RI, Utomo RY, Amalina ND, Ilmawati GPN, Kawaichi M, Meiyanto E. Genistein Enhances Cytotoxic and Antimigratory Activities of Doxorubicin on 4T1 Breast Cancer Cells Through Cell Cycle Arrest and ROS Generation. J App Pharm Sci. 2020; 10(10):095–104.
32. Rahmawati N, Ismail NH, Wahyuni FS, Hamidi D. Cytotoxic Activity, Cell Migration and Apoptosis Effects of Uncaria nervosa Elmer Leaf Fractions on MCF-7 HER 2 Cells. Trop J Nat Prod Res. 2024; 8(6):7494 - 7498.