Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells.

Publisher: Sciendo Country of Publication: Poland NLM ID: 9303678 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1846-9558 (Electronic) Linking ISSN: 13300075 NLM ISO Abbreviation: Acta Pharm Subsets: MEDLINE

Publication: Warsaw, Poland : Sciendo
Original Publication: Zagreb : Croatian Pharmaceutical Society, 1992-

Furocoumarins*/pharmacology ; Furocoumarins*/chemistry ; Furocoumarins*/therapeutic use ; Antineoplastic Agents* ; Moraceae*/chemistry ; Colorectal Neoplasms*/drug therapy; Humans ; Irinotecan ; Cell Line, Tumor

Although the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i . e ., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen ( 1 ) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate ( 2 ) isolated from ethyl acetate fraction of D. foetida (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound 2 exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound 2 and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri: 2 of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound 2 and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound 2 monotherapy, resp). In conclusion, our results identified compound 2 as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.
(© 2024 Supusson Pengnam et al., published by Sciendo.)

D. Hanahan and R. A. Weinberg, Hallmarks of cancer: The next generation, Cell 144 (5) 646–674; https://doi.org/10.1016/j.cell.2011.02.013.
R. L. Siegel, K. D. Miller and A. Jemal, Cancer statistics, 2016, CA Cancer J. Clin . 66 (1) (2016) 7–30; https://doi.org/10.3322/caac.21332.
M. Vanneman and G. Dranoff, Combining immunotherapy and targeted therapies in cancer treatment, Nat. Rev. Cancer 12 (4) (2012) 237–251; https://doi.org/10.1038/nrc3237.
A. Pathak, S. Tanwar, V. Kumar and B. D. Banarjee, Present and future prospect of small molecule & related targeted therapy against human cancer, Vivechan Int. J. Res . 9 (1) (2018) 36–49.
F. A. Fisusi and E. O. Akala, Drug combinations in breast cancer therapy, Pharm. Nanotechnol . 7 (1) (2019) 3–23; https://doi.org/10.2174/2211738507666190122111224.
B. B. Mishra and V. K. Tiwari, Natural products: an evolving role in future drug discovery, Eur. J. Med. Chem . 46 (10) (2011) 4769–4807; https://doi.org/10.1016/j.ejmech.2011.07.057.
G. M. Cragg and D. J. Newman, Plants as a source of anti-cancer agents, J. Ethnopharmacol. 100 (1–2) (2005) 72–79; https://doi.org/10.1016/j.jep.2005.05.011.
F. M. de Man, A. K. L. Goey, R. H. N. van Schaik, R. H. J. Mathijssen and S. Bins, Individualization of irinotecan treatment: A review of pharmacokinetics, pharmacodynamics, and pharmacogenetics, Clin. Pharmacokinet . 57 (10) (2018) 1229–1254; https://doi.org/10.1007/s40262-018-0644-7.
A. B. Benson, A. P. Venook, M. M. Al-Hawary, M. A. Arain, Yi-J. Chen, K. K. Ciombor, S. Cohen, H. S. Cooper, D. Deming, L. Farkas, I. Garrido-Laguna, J. L. Grem, A. Gunn, J. R. Hecht, S. Hoffe, J. Hubbard, S. Hunt, K. L. Johung, N. Kirilcuk, S. Krishnamurthi, W. A. Messersmith, J. Meyerhardt, E. D. Miller, M. F. Mulcahy, S. Nurkin, M. J. Overman, A. Parikh, H. Patel, K. Pedersen, L. Saltz, C. Schneider, D. Shibata, J. M. Skibber, C. T. Sofocleous, E. M. Stoffel, E. Stotsky-Himelfarb, C. G. Willett, K. M. Gregory and L. A. Gurski, Colon cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology, J. Nat. Compreh. Cancer Network 19 (3) (2021) 329–359; https://doi.org/10.6004/jnccn.2021.0012.
A. J. Alonso-Castro, M. L. Villarreal, L. A. Salazar-Olivo, M. Gomez-Sanchez, F. Dominguez and A. Garcia-Carranca, Mexican medicinal plants used for cancer treatment: pharmacological, phyto-chemical and ethnobotanical studies, J. Ethnopharmacol. 133 (3) (2011) 945–972; https://doi.org/10.1016/j.jep.2010.11.055.
N. F. Bussa and A. Belayneh, Traditional medicinal plants used to treat cancer, tumors and inflammatory ailments in Harari Region, Eastern Ethiopia, South Afr. J. Bot . 122 (2019) 360–368; https://doi.org/https://doi.org/10.1016/j.sajb.2019.03.025.
T. Teklehaymanot and M. Giday, Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia, J. Ethnobiol. Ethnomed. 3 (2007) Article ID 12 (11 pages); https://doi.org/10.1186/1746-4269-3-12.
T. Teklehaymanot, Ethnobotanical study of knowledge and medicinal plants used by the people in Dek Island in Ethiopia, J. Ethnopharmacol. 124 (1) (2009) 69–78; https://doi.org/10.1016/j.jep.2009.04.005.
V. Kuete, B. Krusche, M. Youns, I. Voukeng, A. G. Fankam, S. Tankeo, S. Lacmata and T. Efferth, Cytotoxicity of some Cameroonian spices and selected medicinal plant extracts, J. Ethnopharmacol. 134 (3) (2011) 803–812; https://doi.org/10.1016/j.jep.2011.01.035.
F. A. Adem, V. Kuete, A. T. Mbaveng, M. Heydenreich, A. Ndakala, B. Irungu, T. Efferth and A. Yenesew, Cytotoxic benzylbenzofuran derivatives from Dorstenia kameruniana , Fitoterapia 128 (2018) 26–30; https://doi.org/10.1016/j.fitote.2018.04.019.
T. Uchiyama, S. Hara, M. Makino and Y. Fujimoto, seco-Adianane-type triterpenoids from Dorstenia brasiliensis (Moraceae), Phytochemistry 60 (8) (2002) 761–764.
V. Kuete, A. T. Mbaveng, M. Zeino, B. Ngameni, G. D. Kapche, S. F. Kouam, B. T. Ngadjui and T. Efferth, Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells, Phytomedicine 22 (7–8) (2015) 737–743; https://doi.org/10.1016/j.phymed.2015.04.007.
R. Heinke, K. Franke, A. Porzel, L. A. Wessjohann, N. A. Ali and J. Schmidt, Furanocoumarins from Dorstenia foetida , Phytochemistry 72 (9) (2011) 929–934; https://doi.org/10.1016/j.phytochem.2011.03.008.
C. A. Schneider, W. S. Rasband and K. W. Eliceiri, NIH Image to ImageJ: 25 years of image analysis, Nature Meth. 9 (7) (2012) 671–675; https://doi.org/10.1038/nmeth.2089.
P. Kumar, A. Nagarajan and P. D. Uchil, Analysis of cell viability by the MTT assay, Cold Spring Harbor Protoc . 2018 (6) (2018) 469–471; https://doi.org/10.1101/pdb.prot095505.
S. W. Jarantow, E. D. Pisors and M. L. Chiu, Introduction to the use of linear and nonlinear regression analysis in quantitative biological assays, Curr. Prot. 3 (6) (2023) e801; https://doi.org/https://doi.org/10.1002/cpz1.801.
I. V. Bijnsdorp, E. Giovannetti and G. J. Peters, Analysis of drug interactions, Meth. Mol. Biol. 731 (2011) 421–434; https://doi.org/10.1007/978-1-61779-080-5_34.
T. C. Chou, Drug combination studies and their synergy quantification using the Chou-Talalay method, Cancer Res . 70 (2) (2010) 440–446; https://doi.org/10.1158/0008-5472.Can-09-1947.
K. Franke, A. Porzel, M. Masaoud, G. Adam and J. Schmidt, Furanocoumarins from Dorstenia gigas , Phytochemistry 56 (6) (2001) 611–621; https://doi.org/10.1016/s0031-9422(00)00419-2.
B. Ngameni, V. Kuete, I. K. Simo, A. T. Mbaveng, P. K. Awoussong, R. Patnam, R. Roy and B. T. Ngadjui, Antibacterial and antifungal activities of the crude extract and compounds from Dorstenia turbinata (Moraceae), South Afr. J. Bot. 75 (2) (2009) 256–261; https://doi.org/https://doi.org/10.1016/j.sajb.2008.11.006.
J. Jamalis, F. S. M. Yusof, S. Chander, R. A. Wahab, P. B. D, M. Sankaranarayanan, F. Almalki and T. B. Hadda, Psoralen derivatives: Recent advances of synthetic strategy and pharmacological properties, Antiinflamm. Antiallergy Agents Med. Chem . 19 (3) (2020) 222–239; https://doi.org/10.2174/1871523018666190625170802.
Y. Ren, X. Song, Lu Tan, C. Guo, M. Wang, H. Liu, Z. Cao, Y. Li and C. Peng, A review of the pharmacological properties of psoralen, Front. Pharmacol. 11 (2020) Article ID 571535 (18 pages); https://doi.org/10.3389/fphar.2020.571535.
J. Guinney, R. Dienstmann, X. Wang, A. de Reyniès, A. Schlicker, C. Soneson, L. Marisa, P. Roepman, G. Nyamundanda, P. Angelino, B. M. Bot, J. S. Morris, I. M. Simon, S. Gerster, E. Fessler, F. De Sousa E. Melo, E. Missiaglia, H. Ramay, D. Barras, K. Homicsko, D. Maru, G. C. Manyam, B. Broom, V. Boige, B. Perez-Villamil, T. Laderas, R. Salazar, J. W. Gray, D. Hanahan, J. Tabernero, R. Bernards, S. H. Friend, P. Laurent-Puig, J. P. Medema, A. Sadanandam, L. Wessels, M. Delorenzi, S. Kopetz, L. Vermeulen and S. Tejpar, The consensus molecular subtypes of colorectal cancer, Nature Med . 21 (11) (2015) 1350–1356; https://doi.org/10.1038/nm.3967.
R. Dienstmann, L. Vermeulen, J. Guinney, S. Kopetz, S. Tejpar and J. Tabernero, Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer, Nat. Rev. Cancer 17 (2) (2017) 79–92; https://doi.org/10.1038/nrc.2016.126.
K. C. G. Berg, P. W. Eide, I. A. Eilertsen, B. Johannessen, J. Bruun, S. A. Danielsen, M. Bjørnslett, L. A. Meza-Zepeda, M. Eknæs, G. E. Lind, O. Myklebost, R. I. Skotheim, A. Sveen and R. A. Lothe, Multi-omics of 34 colorectal cancer cell lines – a resource for biomedical studies, Mol. Cancer 16 (1) (2017) Article ID 116 (16 pages); https://doi.org/10.1186/s12943-017-0691-y.
A. Sveen, J. Bruun, P. W. Eide, I. A. Eilertsen, L. Ramirez, A. Murumagi, M. Arjama, S. A. Danielsen, K. Kryeziu, E. Elez, J. Tabernero, J. Guinney, H. G. Palmer, A. Nesbakken, O. Kallioniemi, R. Dienstmann and R. A. Lothe, Colorectal cancer consensus molecular subtypes translated to preclinical models uncover potentially targetable cancer cell dependencies, Clin. Cancer Res . 24 (4) (2018) 794–806; https://doi.org/10.1158/1078-0432.ccr-17-1234.
A. Okita, S. Takahashi, K. Ouchi, M. Inoue, M. Watanabe, M. Endo, H. Honda, Y. Yamada and C. Ishioka, Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer, Oncotarget 9 (27) (2018) 18698–18711; https://doi.org/10.18632/oncotarget.24617.

Keywords: 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate; anticancer activity; furanocoumarins; irinotecan; synergism

7673326042 (Irinotecan)
0 (Furocoumarins)
0 (Antineoplastic Agents)

Date Created: 20240330 Date Completed: 20240401 Latest Revision: 20240401

20240401

10.2478/acph-2024-0004

38554381