Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structure Determination of Compounds
2.2. Antiproliferative Activity
2.3. MDR Efflux Pump Inhibitory Activity
2.4. Combination Studies with Doxorubicin
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Mushroom Material
3.3. Extraction and Isolation
3.4. Cell Culture
3.5. Assay for Antiproliferative Effect
3.6. Rhodamine 123 Accumulation Assay
3.7. Checkerboard Combination Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Tang, Y.; Zhao, Z.-Z.; Hu, K.; Feng, T.; Li, Z.-H.; Chen, H.-P.; Liu, J.-K. Irpexolidal Represents a Class of Triterpenoid from the Fruiting Bodies of the Medicinal Fungus Irpex lacteus. J. Org. Chem. 2019, 84, 1845–1852. [Google Scholar] [CrossRef]
- Isaka, M.; Chinthanom, P.; Thummarukcharoen, T.; Boonpratuang, T.; Choowong, W. Highly Modified Lanostane Triterpenes from Fruiting Bodies of the Basidiomycete Tomophagus sp. J. Nat. Prod. 2019, 82, 1165–1176. [Google Scholar] [CrossRef]
- Zhang, J.; Chen, B.; Liang, J.; Han, J.; Zhou, L.; Zhao, R.; Liu, H.; Dai, H. Lanostane Triterpenoids with PTP1B Inhibitory and Glucose-Uptake Stimulatory Activities from Mushroom Fomitopsis pinicola Collected in North America. J. Agric. Food Chem. 2020, 68, 10036–10049. [Google Scholar] [CrossRef]
- Kotlába, F.; Pouzar, Z. Buglossosporus gen. nov.—A new genus of polypores. Czech Mycol. 1966, 20, 81–89. [Google Scholar]
- Ryvarden, L.; Gilbertson, R.L. European Polypores. 2. Meripilus–Tyromyces. Synopsis Fungorum 7; Fungiflora: Oslo, Norway, 1994; Volume 7, pp. 394–743. [Google Scholar]
- Grienke, U.; Zöll, M.; Peintner, U.; Rollinger, J.M. European medicinal polypores—A modern view on traditional uses. J. Ethnopharmacol. 2014, 154, 564–583. [Google Scholar] [CrossRef]
- Han, M.-L.; Chen, Y.-Y.; Shen, L.-L.; Song, J.; Vlasák, J.; Dai, Y.-C.; Cui, B.-K. Taxonomy and phylogeny of the brown-rot fungi: Fomitopsis and its related genera. Fungal Divers. 2016, 80, 343–373. [Google Scholar] [CrossRef]
- Justo, A.; Miettinen, O.; Floudas, D.; Ortiz-Santana, B.; Sjökvist, E.; Lindner, D.; Nakasone, K.; Niemelä, T.; Larsson, K.-H.; Ryvarden, L.; et al. A revised family-level classification of the Polyporales (Basidiomycota). Fungal Biol. 2017, 121, 798–824. [Google Scholar] [CrossRef]
- Ryvarden, L. Neotropical Polypores Part 3, Polyporaceae, Obba-Wrightoporia; Fungiflora: Oslo, Norway, 2016; Volume 36, pp. 445–613. [Google Scholar]
- Szczepkowski, A.; Gierczyk, B.; Kujawa, A. Buglossoporus pulvinus, a rare wood-inhabiting fungus on ancient oak trees in Poland: Ecology, distribution and extinction risk assessment. Balt. For. 2019, 25, 178–186. [Google Scholar] [CrossRef]
- Zhou, L.; Zhang, Y.; Gapter, L.A.; Ling, H.; Agarwal, R.; Ng, K.Y. Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos. Chem. Pharm. Bull. 2008, 56, 1459–1462. [Google Scholar] [CrossRef]
- Rösecke, J.; König, W.A. Constituents of the fungi Daedalea quercina and Daedaleopsis confragosa var. tricolor. Phytochemistry 2000, 54, 757–762. [Google Scholar] [CrossRef]
- Sofrenić, I.; Anđelković, B.; Todorović, N.; Stanojković, T.; Vujisić, L.; Novaković, M.; Milosavljević, S.; Tešević, V. Cytotoxic triterpenoids and triterpene sugar esters from the medicinal mushroom Fomitopsis betulina. Phytochemistry 2021, 181, 112580. [Google Scholar] [CrossRef] [PubMed]
- Peng, X.-R.; Su, H.-G.; Liu, J.-H.; Huang, Y.-J.; Yang, X.-Z.; Li, Z.-R.; Zhou, L.; Qiu, M.-H. C30 and C31 Triterpenoids and Triterpene Sugar Esters with Cytotoxic Activities from Edible Mushroom Fomitopsis pinicola (Sw. Ex Fr.) Krast. J. Agric. Food Chem. 2019, 67, 10330–10341. [Google Scholar] [CrossRef] [PubMed]
- Thappa, R.K.; Agarwal, S.G.; Dhar, K.L.; Atal, C.K. A new triterpenic acid from the wood rotting fungi. Phytochemistry 1981, 20, 1746–1747. [Google Scholar] [CrossRef]
- Zhao, J.; Yang, Y.; Yu, M.; Yao, K.; Luo, X.; Qi, H.; Zhang, G.; Luo, Y. Lanostane-type C(31) triterpenoid derivatives from the fruiting bodies of cultivated Fomitopsis palustris. Phytochemistry 2018, 152, 10–21. [Google Scholar] [CrossRef] [PubMed]
- King, T.J.; Smith, R.W.; Begley, M.J.; Goad, L.J. The stereochemistry of polyporenic acid a methyl ester. Tetrahedron Lett. 1984, 25, 3489–3492. [Google Scholar] [CrossRef]
- Kamo, T.; Asanoma, M.; Shibata, H.; Hirota, M. Anti-inflammatory lanostane-type triterpene acids from Piptoporus betulinus. J. Nat. Prod. 2003, 66, 1104–1106. [Google Scholar] [CrossRef]
- Khalilov, Q.; Li, L.; Liu, Y.; Tohtahon, Z.; Chen, X.; Aisa, H.A.; Yuan, T. Piptolinic acids F-J, five new lanostane-type triterpenoids from Piptoporus betulinus. Nat. Prod. Res. 2019, 33, 3044–3051. [Google Scholar] [CrossRef]
- Isaka, M.; Chinthanom, P.; Suvannakad, R.; Thummarukcharoen, T.; Feng, T.; Liu, J.-K. Fomitopsins I and J, 24-methyl-lanostane triterpenoids from fruiting bodies of the wood-rot basidiomycete Fomitopsis sp. Phytochem. Lett. 2019, 29, 178–181. [Google Scholar] [CrossRef]
- Wangun, H.V.; Berg, A.; Hertel, W.; Nkengfack, A.E.; Hertweck, C. Anti-inflammatory and anti-hyaluronate lyase activities of lanostanoids from Piptoporus betulinus. J. Antibiot. 2004, 57, 755–758. [Google Scholar] [CrossRef]
- Zhang, F.L.; Shi, C.; Sun, L.T.; Yang, H.X.; He, J.; Li, Z.H.; Feng, T.; Liu, J.K. Chemical constituents and their biological activities from the mushroom Pyropolyporus fomentarius. Phytochemistry 2021, 183, 112625. [Google Scholar] [CrossRef]
- Chou, T.-C. Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies. Pharmacol. Rev. 2006, 58, 621. [Google Scholar] [CrossRef] [PubMed]
- Chou, T.-C. Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method. Cancer Res. 2010, 70, 440–446. [Google Scholar] [CrossRef] [PubMed]
1 c | 2 c | 3 a | 4 a | 5 b | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Position | δC Type | δH (J in Hz) | δC Type | δH (J in Hz) | δC Type | δH (J in Hz) | δC Type | δc Type | δH (J in Hz) | ||||||
1 | 35.7 | CH2 | 1.82, m | 36.4 | CH2 | 1.51, m | 30.7 | CH2 | 1.43, m | 30.6 | CH2 | 1.49, m | 31.6 | CH2 | 1.75, m |
1.54, m | 1.09, m | 1.37, m | 1.41, m | 1.55, m | |||||||||||
2 | 36.8 | CH2 | 2.31, dd, (10.0, 8.0) | 28.8 | CH2 | 1.48, m | 23.1 | CH2 | 1.87, m | 23.2 | CH2 | 1.90, m | 24.1 | CH2 | 1.90, m |
2.28, dd, (8.0, 3.4) | 1.67, m | 1.72, m | 1.78, m | ||||||||||||
3 | 216.0 | C | 78.3 | CH | 2.97, m | 77.6 | CH | 4.68, br s | 80.6 | CH | 4.76, br s | 78.4 | CH | 4.97, br s | |
4 | 52.8 | C | 39.7 | C | 36.7 | C | 36.8 | C | 37.4 | C | |||||
5 | 44.3 | CH | 2.17, m | 51.5 | CH | 0.96, m | 45.2 | CH | 1.50, m | 45.3 | CH | 1.47, m | 46.4 | CH | 1.83, m |
6 | 20.2 | CH2 | 1.49, m | 19.1 | CH2 | 1.65, m | 17.8 | CH2 | 1.67, m | 18.0 | CH2 | 1.59, m | 18.8 | CH2 | 1.62, m |
1.44, m | 1.49, m | 1.56, m | 1.49, m | 1.52, m | |||||||||||
7 | 27.2 | CH2 | 2.03, m | 27.2 | CH2 | 2.06, m | 25.8 | CH2 | 2.12, m | 25.9 | CH2 | 2.04, m | 26.8 | CH2 | 2.17, m |
1.93, m | 1.95, m | 2.07, m | 2.12, m | ||||||||||||
8 | 136.6 | C | 135.8 | C | 135.0 | C | 134.2 | C | 135.5 | C | |||||
9 | 134.0 | C | 136.6 | C | 135.1 | C | 134.3 | C | 134.2 | C | |||||
10 | 37.6 | C | 37.8 | C | 36.7 | C | 36.8 | C | 37.5 | C | |||||
11 | 21.4 | CH2 | 1.94, m | 40.5 | CH2 | 2.82, m | 39.9 | CH2 | 2.90, m | 20.9 | CH2 | 2.01, m | 34.9 | CH2 | 2.76, m |
2.49, m | 2.71, m | 2.50, m | |||||||||||||
12 | 30.0 | CH2 | 1.71, m | 210.5 | C | 212.7 | C | 30.9 | CH2 | 1.74, m | 72.5 | CH | 4.27, d (7.6) | ||
1.39, m | 1.69, m | ||||||||||||||
13 | 46.5 | C | 55.0 | C | 54.5 | C | 44.5 | C | 50.5 | C | |||||
14 | 49.4 | C | 60.0 | C | 59.4 | C | 49.9 | C | 50.4 | C | |||||
15 | 44.0 | CH2 | 2.03, m | 30.9 | CH2 | 1.75, m | 30.1 | CH2 | 1.82, m | 30.8 | CH2 | 1.60, m | 33.1 | CH2 | 1.76, m |
1.15, m | 1.20, m | 1.35, m | 1.18, m | 1.25, m | |||||||||||
16 | 77.1 | CH | 3.89, m | 28.6 | CH2 | 1.91, m | 27.8 | CH2 | 2.01, m | 28.2 | CH2 | 1.94, m | 28.7 | CH2 | 2.11, m |
1.29, m | 1.37, m | 1.31, m | 1.40, m | ||||||||||||
17 | 57.3 | CH | 1.96, m | 43.5 | CH | 2.06, m | 42.4 | CH | 2.19, m | 50.3 | CH | 1.50, m | 43.5 | CH | 2.65, m |
18 | 17.8 | CH3 | 0.69, s | 12.9 | CH3 | 0.94, s | 12.6 | CH3 | 1.05, s | 15.7 | CH3 | 0.69, s | 17.2 | CH3 | 0.77, s |
19 | 19.2 | CH3 | 0.95, s | 19.5 | CH3 | 0.98, s | 19.0 | CH3 | 1.08, s | 18.9 | CH3 | 1.00, s | 19.4 | CH3 | 1.03, s |
20 | 48.3 | CH | 2.24, m | 37.7 | CH | 1.18, m | 36.6 | CH | 1.27, m | 36.3 | CH | 1.41, m | 37.3 | CH | 1.53, m |
21 | 177.4 | C | 19.6 | CH3 | 0.78, d (6.4) | 19.0 | CH3 | 0.89, d (5.8) | 18.6 | CH3 | 0.93, m | 18.3 | CH3 | 1.28, m | |
22 | 31.6 | CH2 | 1.92, m | 35.3 | CH2 | 1.53, m | 34.0 | CH2 | 1.62, m | 34.2 | CH2 | 1.58, m | 35.4 | CH2 | 1.77, m |
1.64, m | 1.14, m | 1.27, m | 1.19, m | 1.38, m | |||||||||||
23 | 33.4 | CH2 | 1.96, m | 32.9 | CH2 | 2.14, m | 32.1 | CH2 | 2.21 | 31.7 | CH2 | 2.19, m | 32.7 | CH2 | 2.37, m |
1.87, m | 1.09, m | 2.02 | 2.00, m | 2.17, m | |||||||||||
24 | 156.7 | C | 150.9 | C | 148.5 | C | 148.3 | C | 150.2 | C | |||||
25 | 34.8 | CH | 2.14, m | 46.2 | CH | 2.96, m | 45.1 | CH | 3.17, m | 45.0 | CH | 3.18, q (7.0) | 46.2 | CH | 3.32, q (7.1) |
26 | 22.4 | CH3 | 0.91, d (6.9) | 175.6 | C | 177.7 | C | 179.6 | C | 175.3 | C | ||||
27 | 22.2 | CH3 | 0.92, d (6.9) | 17.0 | CH3 | 1.10, d (7.4) | 16.3 | CH3 | 1.31, d (6.7) | 16.1 | CH3 | 1.31, d (7.0) | 17.1 | CH3 | 1.38, d (7.1) |
28 | 68.3 | CH2 | 3.39, dd (10.2, 2.4) | 28.5 | CH3 | 0.88, s | 27.5 | CH3 | 0.88, s | 27.6 | CH3 | 0.88, s | 28.5 | CH3 | 1.04, s |
3.16, dd (10.2, 2.4) | |||||||||||||||
29 | 17.5 | CH3 | 0.78, s | 16.1 | CH3 | 0.69, s | 21.7 | CH3 | 0.94, s | 21.7 | CH3 | 0.93, m | 22.4 | CH3 | 0.91, s |
30 | 25.3 | CH3 | 1.05, s | 24.3 | CH3 | 0.65, s | 24.1 | CH3 | 0.82, s | 24.2 | CH3 | 0.91, s | 25.7 | CH3 | 1.43, s |
31 | 106.9 | CH2 | 4.61, br s | 110.3 | CH2 | 4.77, br s | 111.1 | CH2 | 4.97, br s | 111.4 | CH2 | 4.97, br s | 111.3 | CH2 | 5.10, br s |
4.71, br s | 4.94, br s | 4.94, br s | 5.06, br s | ||||||||||||
1′ | 170.8 | C | 167.2 | C | 172.4 d | C | |||||||||
2′ | 40.2 | CH2 | 3.64, m | 47.0 d | CH2 | 2.64 d, m | |||||||||
3′ | 170.6 | C | 71.0 d | C | |||||||||||
4′ | 47.0 d | CH2 | 2.64 d, m | ||||||||||||
5′ | 172.4 d | C | |||||||||||||
1′-CH3 | 21.3 | CH3 | 2.07, s | ||||||||||||
3′-CH3 | 27.9 d | CH3 | |||||||||||||
26-CH3 | 52.3 d | CH3 |
Colo 320 (IC50 µmol) | ||
---|---|---|
Compound | Mean | SD |
1 | 85.65 | 1.45 |
2 | 106.20 | 7.14 |
3 | 29.78 | 2.77 |
4 | 69.16 | 7.47 |
5 | 36.55 | 0.91 |
6 | 87.37 | 3.29 |
7 | 61.71 | 3.86 |
8 | 36.18 | 2.73 |
9 | 39.46 | 1.71 |
10 | 48.97 | 1.24 |
11 | 29.74 | 0.36 |
12 | 20.71 | 2.13 |
doxorubicin * | 0.39 | 0.09 |
Compound | conc µmol | FAR |
---|---|---|
1 | 20 | 0.774 |
2 | 20 | 1.051 |
3 | 20 | 4.448 |
4 | 20 | 1.338 |
5 | 20 | 7.611 |
6 | 20 | 0.386 |
7 | 20 | 0.593 |
8 | 20 | 2.079 |
9 | 20 | 0.942 |
10 | 20 | 3.822 |
11 | 20 | 2.491 |
12 | 20 | 2.267 |
Tariquidar a | 0.2 | 15.091 |
DMSO | 2% | 0.402 |
Compound | Best Ratio | CI at ED50 | SD | Interaction |
---|---|---|---|---|
3 | 27.6:1 | 0.601 | 0.049 | synergism |
4 | 64.1:1 | 0.691 | 0.070 | synergism |
7 | 114.5:1 | 0.419 | 0.069 | synergism |
8 | 67.2:1 | 0.574 | 0.069 | synergism |
9 | 586.2:1 | 0.276 | 0.096 | strong synergism |
10 | 90.9:1 | 0.779 | 0.082 | moderate synergism |
11 | 27.6:1 | 0.841 | 0.140 | moderate synergism |
12 | 38.4:1 | 0.608 | 0.032 | synergism |
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Felegyi, K.; Garádi, Z.; Rácz, B.; Tóth, G.; Papp, V.; Boldizsár, I.; Dancsó, A.; Spengler, G.; Béni, S.; Ványolós, A. Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells. J. Fungi 2023, 9, 923. https://doi.org/10.3390/jof9090923
Felegyi K, Garádi Z, Rácz B, Tóth G, Papp V, Boldizsár I, Dancsó A, Spengler G, Béni S, Ványolós A. Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells. Journal of Fungi. 2023; 9(9):923. https://doi.org/10.3390/jof9090923
Chicago/Turabian StyleFelegyi, Kristóf, Zsófia Garádi, Bálint Rácz, Gábor Tóth, Viktor Papp, Imre Boldizsár, András Dancsó, Gabriella Spengler, Szabolcs Béni, and Attila Ványolós. 2023. "Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells" Journal of Fungi 9, no. 9: 923. https://doi.org/10.3390/jof9090923