226
Views
2
CrossRef citations to date
0
Altmetric
Research Article

Fisetin induces apoptosis in human skin cancer cells through downregulating MTH1

, , , &
Pages 7339-7353 | Received 07 Apr 2022, Accepted 27 Aug 2022, Published online: 21 Sep 2022

References

  • Abu Bakar, M. F., Mohamad, M., Rahmat, A., Burr, S. A., & Fry, J. R. (2010). Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan). Food and Chemical Toxicology, 48(6), 1688–1697. https://doi.org/10.1016/j.fct.2010.03.046
  • Ahamad, M. S., Siddiqui, S., Jafri, A., Ahmad, S., Afzal, M., & Arshad, M. (2014). Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. PLoS One, 9(10), e110003. https://doi.org/10.1371/journal.pone.0110003
  • Ahmed, S. A., Rahman, A. A., Elsayed, K. N. M., Abd El-Mageed, H. R., Mohamed, H. S., & Ahmed, S. A. (2021). Cytotoxic activity, molecular docking, pharmacokinetic properties and quantum mechanics calculations of the brown macroalga Cystoseira trinodis compounds. Journal of Biomolecular Structure & Dynamics, 39(11), 3855–3873. https://doi.org/10.1080/07391102.2020.1774418
  • Amawi, H., Ashby, C. R., & Tiwari, A. K. (2017). Cancer chemoprevention through dietary flavonoids: What’s limiting? Chinese Journal of Cancer, 36(1), 1–13. https://doi.org/10.1186/s40880-017-0217-4
  • Arai, Y., Watanabe, S., Kimira, M., Shimoi, K., Mochizuki, R., & Kinae, N. (2000). Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. The Journal of Nutrition, 130(9), 2243–2250. https://doi.org/10.1093/jn/130.9.2243
  • Azizi, M., Ghourchian, H., Yazdian, F., Dashtestani, F., & AlizadehZeinabad, H. (2017). Cytotoxic effect of albumin coated copper nanoparticle on human breast cancer cells of MDA-MB 231. PLoS One, 12(11), e0188639–21. https://doi.org/10.1371/journal.pone.0188639
  • Benhar, M., Engelberg, D., & Levitzki, A. (2002). ROS, stress-activated kinases and stress signaling in cancer. EMBO Reports, 3(5), 420–425. https://doi.org/10.1093/embo-reports/kvf094
  • Best, R. B., Zhu, X., Shim, J., Lopes, P. E. M., Mittal, J., Feig, M., & MacKerell, A. D. (2012). Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ1 and χ2 Dihedral Angles. Journal of Chemical Theory and Computation, 8(9), 3257–3273. https://doi.org/10.1021/ct300400x
  • Bhat, T. A., Nambiar, D., Pal, A., Agarwal, R., & Singh, R. P. (2012). Fisetin inhibits various attributes of angiogenesis in vitro and in vivo-implications for angioprevention. Carcinogenesis, 33(2), 385–393. https://doi.org/10.1093/carcin/bgr282
  • Choudhari, A. S., Mandave, P. C., Deshpande, M., Ranjekar, P., & Prakash, O. (2020). Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in Pharmacology, 10(January), 1–17. https://doi.org/10.3389/fphar.2019.01614
  • Cragg, G. M., Newman, D. J., & Snader, K. M. (1997). Natural products in drug discovery and development. Journal of Natural Products, 60(1), 52–60. https://doi.org/10.1021/np9604893
  • Desai, A., Qazi, G., Ganju, R., El-Tamer, M., Singh, J., Saxena, A., Bedi, Y., Taneja, S., & Bhat, H. (2008). Medicinal plants and cancer chemoprevention. Current Drug Metabolism, 9(7), 581–591. https://doi.org/10.2174/138920008785821657
  • Ding, G., Xu, X., Li, D., Chen, Y., Wang, W., Ping, D., Jia, S., & Cao, L. (2020). Fisetin inhibits proliferation of pancreatic adenocarcinoma by inducing DNA damage via RFXAP/KDM4A-dependent histone H3K36 demethylation. Cell Death and Disease, 11(10), 1-17. https://doi.org/10.1038/s41419-020-03019-2
  • Du, J., Lu, X., Long, Z., Zhang, Z., Zhu, X., Yang, Y., & Xu, J. (2013). In vitro and in vivo anticancer activity of aconitine on melanoma cell line B16. Molecules (Basel, Switzerland), 18(1), 757–767. https://doi.org/10.3390/molecules18010757
  • Fatima, S. W., Imtiyaz, K., Alam Rizvi, M. M., & Khare, S. K. (2021). Microbial transglutaminase nanoflowers as an alternative nanomedicine for breast cancer theranostics. RSC Advances, 11(55), 34613–34630. https://doi.org/10.1039/d1ra04513j
  • Feitelson, M. A., Arzumanyan, A., Kulathinal, R. J., Blain, S. W., Holcombe, R. F., Mahajna, J., Marino, M., Martinez-Chantar, M. L., Nawroth, R., Sanchez-Garcia, I., Sharma, D., Saxena, N. K., Singh, N., Vlachostergios, P. J., Guo, S., Honoki, K., Fujii, H., Georgakilas, A. G., Bilsland, A., … Nowsheen, S. (2015). Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Seminars in Cancer Biology, 35, S25–S54. https://doi.org/10.1016/j.semcancer.2015.02.006
  • Franken, N. A. P., Rodermond, H. M., Stap, J., Haveman, J., & van Bree, C. (2006). Clonogenic assay of cells in vitro. Nature Protocols, 1(5), 2315–2319. https://doi.org/10.1038/nprot.2006.339
  • Fridlender, M., Kapulnik, Y., & Koltai, H. (2015). Plant derived substances with anti-cancer activity: From folklore to practice. Frontiers in Plant Science, 6, 799. https://doi.org/10.3389/fpls.2015.00799
  • Fujikawa, K., Kamiya, H., Yakushiji, H., Nakabeppu, Y., & Kasai, H. (2001). Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP. Nucleic Acids Research, 29(2), 449–454. Doi: 10.1093/Nar/29.2.449
  • Gad, H., Koolmeister, T., Jemth, A.-S., Eshtad, S., Jacques, S. A., Ström, C. E., Svensson, L. M., Schultz, N., Lundbäck, T., Einarsdottir, B. O., Saleh, A., Göktürk, C., Baranczewski, P., Svensson, R., Berntsson, R. P.-A., Gustafsson, R., Strömberg, K., Sanjiv, K., Jacques-Cordonnier, M.-C., … Helleday, T. (2014). MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature, 508(7495), 215–221. https://doi.org/10.1038/nature13181
  • Haddad, A. Q., Venkateswaran, V., Viswanathan, L., Teahan, S. J., Fleshner, N. E., Klotz, L. H., Haddad, A. Q., Venkateswaran, V., Viswanathan, L., Teahan, S. J., & Fleshner NE, K. L. (2006). Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer and Prostatic Diseases, 9(1), 68–76. https://doi.org/10.1038/sj.pcan.4500845
  • Helleday, T. (2014). Cancer phenotypic lethality, exemplified by the non-essential MTH1 enzyme being required for cancer survival. Annals of Oncology, 25(7), 1253–1255. (https://doi.org/10.1093/annonc/mdu158
  • Huber, K. V. M., Salah, E., Radic, B., Gridling, M., Elkins, J. M., Stukalov, A., Jemth, A.-S., Göktürk, C., Sanjiv, K., Strömberg, K., Pham, T., Berglund, U. W., Colinge, J., Bennett, K. L., Loizou, J. I., Helleday, T., Knapp, S., & Superti-Furga, G. (2014). Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature, 508(7495), 222–227. https://doi.org/10.1038/nature13194
  • Ichikawa, J., Tsuchimoto, D., Oka, S., Ohno, M., Furuichi, M., Sakumi, K., & Nakabeppu, Y. (2008). Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death. DNA Repair, 7(3), 418–430. https://doi.org/10.1016/j.dnarep.2007.11.007
  • Imran, M., Iqubal, M. K., Imtiyaz, K., Saleem, S., Mittal, S., Rizvi, M. M. A., Ali, J., & Baboota, S. (2020). Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. International Journal of Pharmaceutics, 587(March), 119705. https://doi.org/10.1016/j.ijpharm.2020.119705
  • Jang, D. K., Lee, I. S., Shin, H. S., & Yoo, H. M. (2020). 2Α-hydroxyeudesma-4,11(13)-dien-8Β,12-olide isolated from Inula britannica induces apoptosis in diffuse large B-cell lymphoma cells. Biomolecules, 10(2), 324. https://doi.org/10.3390/biom10020324
  • Jia, S., Xu, X., Zhou, S., Chen, Y., Ding, G., & Cao, L. (2019). Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways. In Cell Death and Disease, 10(2), 1-15. https://doi.org/10.1038/s41419-019-1366-y
  • Kabsch, W. (1976). Kabsch_1976. Acta Crystallographica Section A, 32(5), 922–923. https://doi.org/10.1107/S0567739476001873
  • Kamath-Loeb, A. S., Hizi, A., Kasai, H., & Loeb, L. A. (1997). Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases. The Journal of Biological Chemistry, 272(9), 5892–5898. https://doi.org/10.1074/jbc.272.9.5892
  • Kashyap, D., Sharma, A., Sak, K., Tuli, H. S., Buttar, H. S., & Bishayee, A. (2018). Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sciences, 194, 75–87. https://doi.org/10.1016/j.lfs.2017.12.005
  • Katafuchi, A., & Nohmi, T. (2010). DNA polymerases involved in the incorporation of oxidized nucleotides into DNA: Their efficiency and template base preference. Mutation Research, 703(1), 24–31. https://doi.org/10.1016/j.mrgentox.2010.06.004
  • Kettle, J. G., Alwan, H., Bista, M., Breed, J., Davies, N. L., Eckersley, K., Fillery, S., Foote, K. M., Goodwin, L., Jones, D. R., Käck, H., Lau, A., Nissink, J. W. M., Read, J., Scott, J. S., Taylor, B., Walker, G., Wissler, L., & Wylot, M. (2016). Potent and selective inhibitors of MTH1 probe its role in cancer cell survival. Journal of Medicinal Chemistry, 59(6), 2346–2361. https://doi.org/10.1021/acs.jmedchem.5b01760
  • Khan, N., Afaq, F., Syed, D. N., & Mukhtar, H. (2008). Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. Carcinogenesis, 29(5), 1049–1056. https://doi.org/10.1093/carcin/bgn078
  • Kim, J. A., Lee, S., Kim, D. E., Kim, M., Kwon, B. M., & Han, D. C. (2015). Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis, 36(6), 696–706. https://doi.org/10.1093/carcin/bgv045
  • Kroemer, G., Galluzzi, L., & Brenner, C. (2007). Mitochondrial membrane permeabilization in cell death. Physiological Reviews, 87(1), 99–163. https://doi.org/10.1152/physrev.00013.2006
  • Kufareva, I., & Abagyan, R. (2012). Methods of protein structure comparison. Methods in Molecular Biology (Clifton, N.J.), 857, 231–257. https://doi.org/10.1007/978-1-61779-588-6_10
  • Lall, R. K., Adhami, V. M., & Mukhtar, H. (2016). Dietary flavonoid fisetin for cancer prevention and treatment. Molecular Nutrition & Food Research, 60(6), 1396–1405. https://doi.org/10.1002/mnfr.201600025
  • Lall, R. K., Syed, D. N., Khan, M. I., Adhami, V. M., Gong, Y., Lucey, J. A., & Mukhtar, H. (2016). Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis. Carcinogenesis, 37(9), 918–928. https://doi.org/10.1093/carcin/bgw071
  • Leiter, U., Keim, U., & Garbe, C. (2020). Epidemiology of skin cancer: Update 2019. Advances in Experimental Medicine and Biology, 1268, 123–139. https://doi.org/10.1007/978-3-030-46227-7_6
  • Li, R., Liang, H. Y., Li, M. Y., Lin, C. Y., Shi, M. J., & Zhang, X. J. (2014). Interference of fisetin with targets of the nuclear factor-kappaB signal transduction pathway activated by Epstein-Barr virus encoded latent membrane protein 1. Asian Pacific Journal of Cancer Prevention, 15(22), 9835–9839. http://www.ncbi.nlm.nih.gov/pubmed/25520114
  • Lin, S. R., Chang, C. H., Hsu, C. F., Tsai, M. J., Cheng, H., Leong, M. K., Sung, P. J., Chen, J. C., & Weng, C. F. (2020). Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. British Journal of Pharmacology, 177(6), 1409–1423. https://doi.org/10.1111/bph.14816
  • Ly, J. D., Grubb, D. R., & Lawen, A. (2003). The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis, 8(2), 115–128. https://doi.org/10.1023/A:1022945107762
  • Manzoor, S., Bashir, D. J., Imtiyaz, K., Rizvi, M. M. A., Ahamad, I., Fatma, T., Agarwal, N. B., Arora, I., & Samim, M. (2021). Biofabricated platinum nanoparticles: Therapeutic evaluation as a potential nanodrug against breast cancer cells and drug-resistant bacteria. RSC Advances, 11(40), 24900–24916. https://doi.org/10.1039/d1ra03133c
  • Mukhtar, E., Adhami, V. M., Siddiqui, I. A., Verma, A. K., & Mukhtar, H. (2016). Fisetin enhances chemotherapeutic effect of cabazitaxel against human prostate cancer cells. Molecular Cancer Therapeutics, 15(12), 2863–2874. https://doi.org/10.1158/1535-7163.MCT-16-0515
  • Nakabeppu, Y. (2001). Molecular genetics and structural biology of human MutT homolog, MTH1. Mutation Research, 477(1–2), 59–70. https://doi.org/10.1016/S0027-5107(01)00096-3
  • Nakabeppu, Y. (2014). Cellular levels of 8-oxoguanine in either DNA or the nucleotide pool play pivotal roles in carcinogenesis and survival of cancer cells. International Journal of Molecular Sciences, 15(7), 12543–12557. https://doi.org/10.3390/ijms150712543
  • Nakabeppu, Y., Ohta, E., & Abolhassani, N. (2017). MTH1 as a nucleotide pool sanitizing enzyme: Friend or foe? Free Radical Biology & Medicine, 107, 151–158. https://doi.org/10.1016/j.freeradbiomed.2016.11.002
  • Nguyen, N. H., Hoai Ta, Q. T., Pham, Q. T., Han Luong, T. N., Phung, V. T., Duong, T. H., & Vo, V. G. (2020). Anticancer activity of novel plant extracts and compounds from Adenosma bracteosum (Bonati) in human lung and liver cancer cells. Molecules, 25(12), 2912. https://doi.org/10.3390/molecules25122912
  • Ow, Y. L. P., Green, D. R., Hao, Z., & Mak, T. W. (2008). Cytochrome c: Functions beyond respiration. Nature Reviews. Molecular Cell Biology, 9(7), 532–542. https://doi.org/10.1038/nrm2434
  • Pandit, A. H., Mazumdar, N., Imtiyaz, K., Rizvi, M. M. A., Ahmad, S., Hussain, A., Mazumdar, N., Imtiyaz, K., Moshahid, M., Rizvi, A., & Ahmad, S. (2019). Periodate-modified gum arabic cross-linked PVA hydrogels: A promising approach toward photoprotection and sustained delivery of folic acid. ACS Omega, 4(14), 16026–16036. https://doi.org/10.1021/acsomega.9b02137
  • Pelicano, H., Carney, D., & Huang, P. (2004). ROS stress in cancer cells and therapeutic implications. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy, 7(2), 97–110. https://doi.org/10.1016/j.drup.2004.01.004
  • Rai, P., Young, J. J., Burton, D. G. A., Giribaldi, M. G., Onder, T. T., & Weinberg, R. A. (2011). Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence. Oncogene, 30(12), 1489–1496. https://doi.org/10.1038/onc.2010.520
  • Rai, P. (2012). Human Mut T homolog 1 (MTH1): A roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS. Small GTPases, 3(2), 120–125. https://doi.org/10.4161/sgtp.19556
  • Rai, P., Onder, T. T., Young, J. J., McFaline, J. L., Pang, B., Dedon, P. C., & Weinberg, R. A. (2009). Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence. Proceedings of the National Academy of Sciences of the United States of America, 106(1), 169–174. https://doi.org/10.1073/pnas.0809834106
  • Ramsey, M. R., & Sharpless, N. E. (2006). ROS as a tumour suppressor? Nature Cell Biology, 8(11), 1213–1215. (https://doi.org/10.1038/ncb1106-1213
  • Rizvi, S. M., Shazi, S., & Mohd, H. (2013). A simple click by click protocol to perform docking. EXCLI Journal, 12, 831–857.  
  • Rundle, C. W., Militello, M., Barber, C., Presley, C. L., Rietcheck, H. R., & Dellavalle, R. P. (2020). Epidemiologic burden of skin cancer in the US and worldwide. Current Dermatology Reports, 9(4), 309–322. https://doi.org/10.1007/s13671-020-00311-4
  • Sak, K. (2012). Chemotherapy and dietary phytochemical agents. Chemotherapy Research and Practice, 2012, 282511–282570. https://doi.org/10.1155/2012/282570
  • Sak, K. (2014). Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacognosy Reviews, 8(16), 122–146. https://doi.org/10.4103/0973-7847.134247
  • Sakai, Y., Furuichi, M., Takahashi, M., Mishima, M., Iwai, S., Shirakawa, M., & Nakabeppu, Y. (2002). A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1. The Journal of Biological Chemistry, 277(10), 8579–8587. https://doi.org/10.1074/JBC.M110566200
  • Sakumi, K., Tominaga, Y., Furuichi, M., Xu, P., Tsuzuki, T., Sekiguchi, M., & Nakabeppu, Y. (2003). Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption. Cancer Research, 63(5), 902–905.
  • Samaranayake, G. J., Huynh, M., & Rai, P. (2017). MTH1 as a chemotherapeutic target: The elephant in the room. Cancers, 9(12), 15–47. https://doi.org/10.3390/cancers9050047
  • Saraste, A., & Pulkki, K. (2000). Morphologic and biochemical hallmarks of apoptosis. Cardiovascular Research, 45(3), 528–537. https://doi.org/10.1016/S0008-6363(99)00384-3
  • Schumacker, P. T. (2006). Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell, 10(3), 175–176. https://doi.org/10.1016/j.ccr.2006.08.015
  • Sekiguchi, M., Mo, J. Y., & Maki, H. (1992). Molecular mechanisms for controlling spontaneous and induced mutagenesis. Nucleic Acids Symposium Series, 27, 101–102.
  • Sekiguchi, M., & Tsuzuki, T. (2002). Oxidative nucleotide damage: Consequences and prevention. In Oncogene, 21(58), 8895–8904. (https://doi.org/10.1038/sj.onc.1206023
  • Seo, S. H., & Jeong, G. S. (2015). Fisetin inhibits TNF-α-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression. International Immunopharmacology, 29(2), 246–253. (https://doi.org/10.1016/j.intimp.2015.11.014
  • Sithara, T., Arun, K. B., Syama, H. P., Reshmitha, T. R., & Nisha, P. (2017). Morin inhibits proliferation of SW480 colorectal cancer cells by inducing apoptosis mediated by reactive oxygen species formation and uncoupling of warburg effect. Frontiers in Pharmacology, 8, 640. https://doi.org/10.3389/fphar.2017.00640
  • Smith, M. L., Murphy, K., Doucette, C. D., Greenshields, A. L., & Hoskin, D. W. (2016). The dietary flavonoid fisetin causes cell cycle arrest, caspase-dependent apoptosis, and enhanced cytotoxicity of chemotherapeutic drugs in triple-negative breast cancer cells. Journal of Cellular Biochemistry, 117(8), 1913–1925. https://doi.org/10.1002/jcb.25490
  • Srinivasan, R., Natarajan, D., Subramaniam Shivakumar, M., & Nagamurugan, N. (2016). Isolation of Fisetin from Elaeagnus indica Serv. Bull. (Elaeagnaceae) with antioxidant and antiproliferative activity. Free Radicals and Antioxidants, 6(2), 145–150. https://doi.org/10.5530/fra.2016.2.3
  • Suh, Y., Afaq, F., Johnson, J. J., & Mukhtar, H. (2009). A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-κB-signaling pathways. Carcinogenesis, 30(2), 300–307. https://doi.org/10.1093/carcin/bgn269
  • Sundarraj, K., Raghunath, A., & Perumal, E. (2018). A review on the chemotherapeutic potential of fisetin: In vitro evidences. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 97, 928–940. https://doi.org/10.1016/j.biopha.2017.10.164
  • Syed, D. N., Adhami, V. M., Khan, N., Khan, M. I., & Mukhtar, H. (2016). Exploring the molecular targets of dietary flavonoid fisetin in cancer. Seminars in Cancer Biology, 40–41(41), 130–140. https://doi.org/10.1016/j.semcancer.2016.04.003
  • Syed, D. N., Suh, Y., Afaq, F., & Mukhtar, H. (2008). Dietary agents for chemoprevention of prostate cancer. Cancer Letters, 265(2), 167–176. https://doi.org/10.1016/J.CANLET.2008.02.050
  • Tarahovsky, Y. S., Kim, Y. A., Yagolnik, E. A., & Muzafarov, E. N. (2014). Flavonoid–membrane interactions: Involvement of flavonoid–metal complexes in raft signaling. Biochimica et Biophysica Acta, 1838(5), 1235–1246. https://doi.org/10.1016/J.BBAMEM.2014.01.021
  • Toosi, K. (2014). NIH public access. Bone, 23(1), 1–7. https://doi.org/10.1016/j.devcel.2011.06.017.Mitochondria
  • Touil, Y. S., Seguin, J., Scherman, D., & Chabot, G. G. (2011). Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemotherapy and Pharmacology, 68(2), 445–455. https://doi.org/10.1007/s00280-010-1505-8
  • Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc.21334
  • Usman, M., Usman, M., Khan, W. R., Yousaf, N., Akram, S., & Murtaza, G. (2022). Exploring the phytochemicals and anti-cancer potential of the members of fabaceae family : A comprehensive review. Molecules 27(12), 2713863. https://doi.org/10.3390/molecules27123863
  • Viñas, P., Martínez-Castillo, N., Campillo, N., & Hernández-Córdoba, M. (2011). Directly suspended droplet microextraction with in injection-port derivatization coupled to gas chromatography-mass spectrometry for the analysis of polyphenols in herbal infusions, fruits and functional foods. Journal of Chromatography. A, 1218(5), 639–646. https://doi.org/10.1016/j.chroma.2010.12.026
  • Wahi, D., Soni, D., & Grover, A. (2021). A double-edged sword: The anti-cancer effects of emodin by inhibiting the redox-protective protein MTH1 and augmenting ROS in NSCLC. Journal of Cancer, 12(3), 652–681. https://doi.org/10.7150/jca.41160
  • Wang, C., & Youle, R. J. (2009). The role of mitochondria in apoptosis. Annual Review of Genetics, 43, 95–118. https://doi.org/10.1146/annurev-genet-102108-134850
  • Yin, Y., & Chen, F. (2020). Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives. Acta Pharmaceutica Sinica B, 10(12), 2259–2271. https://doi.org/10.1016/j.apsb.2020.02.012
  • Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., McGuckian, C., Wade, E. A., Kato, J. I., Grassi, D., Wentworth, M., Burd, C. E., Arriaga, E. A., Ladiges, W. L., Tchkonia, T., … Niedernhofer, L. J. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18–28. https://doi.org/10.1016/j.ebiom.2018.09.015
  • Zeya, B., Nafees, S., Imtiyaz, K., Uroog, L., Fakhri, K. U., & Rizvi, M. M. A. (2021). Diosmin in combination with naringenin enhances apoptosis in colon cancer cells. Oncology Reports, 47(1) https://doi.org/10.3892/or.2021.8215
  • Zhang, Y., Du, Y., Le, W., Wang, K., Kieffer, N., & Zhang, J. (2011). Redox control of the survival of healthy and diseased cells. Antioxidants & Redox Signaling, 15(11), 2867–2908. https://doi.org/10.1089/ars.2010.3685
  • Zhao, M., Mydlarz, W. K., Zhou, S., & Califano, J. (2008). Head and neck cancer cell lines are resistant to mitochondrial-depolarization-induced apoptosis. Journal for Oto-Rhino-Laryngology and Its Related Specialties, 70(4), 257–263. https://doi.org/10.1159/000133280
  • Zhou, W., Ma, L., Yang, J., Qiao, H., Li, L., Guo, Q., Ma, J., Zhao, L., Wang, J., Jiang, G., Wan, X., Adam Goscinski, M., Ding, L., Zheng, Y., Li, W., Liu, H., Suo, Z., & Zhao, W. (2019). Potent and specific MTH1 inhibitors targeting gastric cancer. Cell Death and Disease, 10(6) https://doi.org/10.1038/s41419-019-1665-3

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.