A combined in vitro and molecular dynamics simulation studies unveil the molecular basis of the anticancer potential of piperine targeting AKT1 against prostate cancer

References

• Ahmed, S., Ali, M. C., Ruma, R. A., Mahmud, S., Paul, G. K., Saleh, M. A., Alshahrani, M. M., Obaidullah, A. J., Biswas, S. K., Rahman, M. M., Rahman, M. M., & Islam, M. R. (2022). Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (Piper betle L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes. Molecules, )27(14), 4526. https://doi.org/10.3390/molecules27144526
   PubMed Web of Science ®Google Scholar
• Alley, M. C., Scudiero, D. A., Monks, A., Czerwinski, M. J., Shoemaker, R. H., & Boyd, M. R. (1986). Validation of an automated microculture tetrazolium assay (MTA) to assess growth and drug sensitivity of human-tumor cell-lines. In Proceedings of the American Association for Cancer Research, 27, 389–389.
   Google Scholar
• Al-Mamgani, A., Lebesque, J. V., Heemsbergen, W. D., Tans, L., Kirkels, W. J., Levendag, P. C., & Incrocci, L. (2010). Controversies in the treatment of high-risk prostate cancer-what is the optimal combination of hormonal therapy and radiotherapy: A review of literature. The Prostate, 70(7), 701–709. https://doi.org/10.1002/pros.21102
   PubMed Web of Science ®Google Scholar
• Altomare, D. A., & Testa, J. R. (2005). Perturbations of the AKT signaling pathway in human cancer. Oncogene, 24(50), 7455–7464. https://doi.org/10.1038/sj.onc.1209085
   PubMed Web of Science ®Google Scholar
• Aung, T. N., Qu, Z., Kortschak, R. D., & Adelson, D. L. (2017). Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action. International Journal of Molecular Sciences, 18(3), 656. https://doi.org/10.3390/ijms18030656
   PubMed Web of Science ®Google Scholar
• Baker, N. A., Sept, D., Joseph, S., Holst, M. J., & McCammon, J. A. (2001). Electrostatics of nanosystems: Application to microtubules and the ribosome. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10037–10041. https://doi.org/10.1073/pnas.181342398
   PubMed Web of Science ®Google Scholar
• Baskić, D., Popović, S., Ristić, P., & Arsenijević, N. N. (2006). Analysis of cycloheximide-induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biology International, 30(11), 924–932. https://doi.org/10.1016/j.cellbi.2006.06.016
   PubMed Web of Science ®Google Scholar
• Benson, N. C., & Daggett, V. (2012). A comparison of multiscale methods for the analysis of molecular dynamics simulations. The Journal of Physical Chemistry. B, 116(29), 8722–8731. https://doi.org/10.1021/jp302103t
   PubMed Web of Science ®Google Scholar
• Best, R. B., Zhu, X., Shim, J., Lopes, P. E., Mittal, J., Feig, M., & Mackerell, A. D. Jr (2012). Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles. Journal of Chemical Theory and Computation, 8(9), 3257–3273. https://doi.org/10.1021/ct300400x
   PubMed Web of Science ®Google Scholar
• Caplan, A., & Kratz, A. (2002). Prostate-specific antigen and the early diagnosis of prostate cancer. American Journal of Clinical Pathology, 117 Suppl, S104–S108. https://doi.org/10.1309/C4UN-12LK-43HP-JXY3
   PubMedGoogle Scholar
• da Silva, T. U., Pougy, K. C., Albuquerque, M. G., da Silva Lima, C. H., & Machado, S. P. (2022). Development of parameters compatible with the CHARMM36 force field for [Fe4S4] 2+ clusters and molecular dynamics simulations of adenosine-5’-phosphosulfate reductase in GROMACS 2019. Journal of Biomolecular Structure and Dynamics. 40(8), 3481–3491. https://doi.org/10.1080/07391102.2020.1847687
   PubMed Web of Science ®Google Scholar
• Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N· log (N) method for Ewald sums in large systems. Journal of Chemical Physics. 98(12), 10089–10092. https://doi.org/10.1063/1.464397
   Web of Science ®Google Scholar
• Ekor, M. (2014). The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4, 177. https://doi.org/10.3389/fphar.2013.00177
   PubMed Web of Science ®Google Scholar
• de Souza, A. S., Pacheco, B. D. C., Pinheiro, S., Muri, E. M. F., Dias, L. R. S., Lima, C. H. S., Garrett, R., de Moraes, M. B. M., de Souza, B. E. G., & Puzer, L. (2019). 3-Acyltetramic acids as a novel class of inhibitors for human kallikreins 5 and 7. Bioorganic & Medicinal Chemistry Letters, 29(9), 1094–1098. https://doi.org/10.1016/j.bmcl.2019.02.031
   PubMed Web of Science ®Google Scholar
• Golo, V. L., & Shaĭtan, K. V. (2002). Dynamic attractor for the Berendsen thermostat an the slow dynamics of biomacromolecules. Biofizika, 47(4), 611–617.
   PubMed Web of Science ®Google Scholar
• Grant, O. C., Montgomery, D., Ito, K., & Woods, R. J. (2020). Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Scientific Reports, 10(1), 14991. https://doi.org/10.1038/s41598-020-71748-7
   PubMed Web of Science ®Google Scholar
• Helal, M. A., Shouman, S., Abdelwaly, A., Elmehrath, A. O., Essawy, M., Sayed, S. M., Saleh, A. H., & El-Badri, N. (2022). Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia. Journal of Biomolecular Structure & Dynamics, 40(3), 1109–1119. https://doi.org/10.1080/07391102.2020.1822208
   PubMed Web of Science ®Google Scholar
• Hess, B., Bekker, H., Berendsen, H. J., & Fraaije, J. G. (1997). LINCS: A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18(12), 1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
   Web of Science ®Google Scholar
• Izadi, S., Anandakrishnan, R., & Onufriev, A. V. (2014). Building Water Models: A Different Approach. The Journal of Physical Chemistry Letters, 5(21), 3863–3871. https://doi.org/10.1021/jz501780a
   PubMed Web of Science ®Google Scholar
• Ji, M., Wang, W., Yan, W., Chen, D., Ding, X., & Wang, A. (2017). Dysregulation of AKT1, a miR-138 target gene, is involved in the migration and invasion of tongue squamous cell carcinoma. Journal of Oral Pathology & Medicine : official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 46(9), 731–737. https://doi.org/10.1111/jop.12551
   PubMed Web of Science ®Google Scholar
• Kanase, H. R., & Singh, K. N. M. (2018). Marine pharmacology: Potential, challenges, and future in India. Journal of Medical Sciences, 38(2), 49. https://doi.org/10.4103/jmedsci.jmedsci_126_17
   Google Scholar
• Karplus, M., & Petsko, G. A. (1990). Molecular dynamics simulations in biology. Nature, 347(6294), 631–639. https://doi.org/10.1038/347631a0
   PubMed Web of Science ®Google Scholar
• Kesarwani, K., Gupta, R., & Mukerjee, A. (2013). Bioavailability enhancers of herbal origin: An overview. Asian Pacific Journal of Tropical Biomedicine, 3(4), 253–266. https://doi.org/10.1016/S2221-1691(13)60060-X
   PubMedGoogle Scholar
• Kunnumakkara, A. B., Koca, C., Dey, S., Gehlot, P., Yodkeeree, S., Danda, D., & Aggarwal, B. B. (2009). Traditional uses of spices: An overview. Molecular Targets and Therapeutic Uses of Spices: Modern Uses for Ancient Medicine, 1–24.
   Google Scholar
• Likic, V. A., Gooley, P. R., Speed, T. P., & Strehler, E. E. (2005). A statistical approach to the interpretation of molecular dynamics simulations of calmodulin equilibrium dynamics. Protein Science : A Publication of the Protein Society, 14(12), 2955–2963. https://doi.org/10.1110/ps.051681605
   PubMed Web of Science ®Google Scholar
• Liu, K., Liu, P. C., Liu, R., & Wu, X. (2015). Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Medical Science Monitor Basic Research, 21, 15–20. https://doi.org/10.12659/MSMBR.893327
   PubMed Web of Science ®Google Scholar
• Liu, K., Watanabe, E., & Kokubo, H. (2017). Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations. Journal of Computer-Aided Molecular Design, 31(2), 201–211. https://doi.org/10.1007/s10822-016-0005-2
   PubMed Web of Science ®Google Scholar
• Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nature Reviews. Drug Discovery, 8(8), 627–644. https://doi.org/10.1038/nrd2926
   PubMed Web of Science ®Google Scholar
• Lotfizadeh, R., Sepehri, H., Attari, F., & Delphi, L. (2020). Flavonoid Calycopterin Induces Apoptosis in Human Prostate Cancer Cells In-vitro. Iranian Journal of Pharmaceutica Lresearch: IJPR, 19(3), 391–401. https://doi.org/10.22037/ijpr.2020.113410.14283
   PubMedGoogle Scholar
• Ma, L., He, H., Jiang, K., Jiang, P., He, H., Feng, S., Chen, K., Shao, J., & Deng, G. (2020). FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemo sensitivity in prostate cancer. Aging, 12(7), 6352–6369. https://doi.org/10.18632/aging.103030
   PubMedGoogle Scholar
• Melmed, G. Y., Kwan, L., Reid, K., & Litwin, M. S. (2002). Quality of life at the end of life: Trends in patients with metastatic prostate cancer. Urology, 59(1), 103–109. https://doi.org/10.1016/s0090-4295(01)01457-1
   PubMed Web of Science ®Google Scholar
• Ouyang, D. Y., Zeng, L. H., Pan, H., Xu, L. H., Wang, Y., Liu, K. P., & He, X. H. (2013). Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 60, 424–430. https://doi.org/10.1016/j.fct.2013.08.007
   PubMed Web of Science ®Google Scholar
• Pal, A., Tapadar, P., & Pal, R. (2021). Exploring the Molecular Mechanism of Cinnamic Acid-Mediated Cytotoxicity in Triple Negative MDA-MB-231 Breast Cancer Cells. Anti-Cancer Agents in Medicinal Chemistry, 21(9), 1141–1150. https://doi.org/10.2174/1871520620666200807222248
   PubMedGoogle Scholar
• Páll, S., & Hess, B. (2013). A flexible algorithm for calculating pair interactions on SIMD architectures. Computer Physics Communications, 184(12), 2641–2650. https://doi.org/10.1016/j.cpc.2013.06.003
   Web of Science ®Google Scholar
• Pirolli, D., Sciandra, F., Bozzi, M., Giardina, B., Brancaccio, A., & De Rosa, M. C. (2014). Insights from molecular dynamics simulations: Structural basis for the V567D mutation-induced instability of zebrafish alpha-dystroglycan and comparison with the murine model. PloS One, 9(7), e103866. https://doi.org/10.1371/journal.pone.0103866
   PubMed Web of Science ®Google Scholar
• Prakash, N., Hanumanthappa, M., Preema, K. A., & Vijayalaksmi, V. (2022). Investigating Drug-Target Interactions of Piperine in Prostate Cancer using Network Pharmacology and Docking studies. Research Journal of Biotechnology, 17(10), 32–42. https://doi.org/10.25303/1710rjbt32042
   Web of Science ®Google Scholar
• Rather, R. A., & Bhagat, M. (2018). Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities. Frontiers in Cell and Developmental Biology, 6, 10. https://doi.org/10.3389/fcell.2018.00010
   PubMed Web of Science ®Google Scholar
• Riggio, M., Perrone, M. C., Polo, M. L., Rodriguez, M. J., May, M., Abba, M., Lanari, C., & Novaro, V. (2017). AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins. Scientific Reports, 7, 44244. https://doi.org/10.1038/srep44244
   PubMed Web of Science ®Google Scholar
• Roscigno, M., Sangalli, M., Mazzoccoli, B., Scattoni, V., Da Pozzo, L., & Rigatti, P. (2005). Medical therapy of prostate cancer. A review. Minerva Urologica e Nefrologica = the Italian Journal of Urology and Nephrology, 57(2), 71–84.
   PubMedGoogle Scholar
• Ross, G. A., Rustenburg, A. S., Grinaway, P. B., Fass, J., & Chodera, J. D. (2018). Biomolecular Simulations under Realistic Macroscopic Salt Conditions. The Journal of Physical Chemistry. B, 122(21), 5466–5486. https://doi.org/10.1021/acs.jpcb.7b11734
   PubMed Web of Science ®Google Scholar
• Sadiq, S. K., Wright, D., Watson, S. J., Zasada, S. J., Stoica, I., & Coveney, P. V. (2008). Automated molecular simulation based binding affinity calculator for ligand-bound HIV-1 proteases. Journal of Chemical Information and Modeling, 48(9), 1909–1919. https://doi.org/10.1021/ci8000937
   PubMed Web of Science ®Google Scholar
• Sahai, R., Bhattacharjee, A., Shukla, V. N., Yadav, P., Hasanain, M., Sarkar, J., Narender, T., & Mitra, K. (2020). Gedunin isolated from the mangrove plant Xylocarpus granatum exerts its anti-proliferative activity in ovarian cancer cells through G2/M-phase arrest and oxidative stress-mediated intrinsic apoptosis. Apoptosis : An International Journal on Programmed Cell Death, 25(7-8), 481–499. https://doi.org/10.1007/s10495-020-01605-5
   PubMed Web of Science ®Google Scholar
• Samykutty, A., Shetty, A. V., Dakshinamoorthy, G., Bartik, M. M., Johnson, G. L., Webb, B., Zheng, G., Chen, A., Kalyanasundaram, R., & Munirathinam, G. (2013). Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells. PloS One, 8(6), e65889. https://doi.org/10.1371/journal.pone.0065889
   PubMed Web of Science ®Google Scholar
• Schreiner, W., Karch, R., Knapp, B., & Ilieva, N. (2012). Relaxation estimation of RMSD in molecular dynamics immunosimulations. Computational and Mathematical Methods in Medicine, 2012, 173521. https://doi.org/10.1155/2012/173521
   PubMed Web of Science ®Google Scholar
• Selvan, G. T., Ashok, A. K., Rao S J, A., Gollapalli, P., R, V., N, S. K., & Chaudhury, N. K. (2022). Nrf2-regulated antioxidant response ameliorating ionizing radiation-induced damages explored through in vitro and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics, 1–13. Advance online publication. https://doi.org/10.1080/07391102.2022.2137245
   Web of Science ®Google Scholar
• Selvendiran, K., Banu, S. M., & Sakthisekaran, D. (2004). Protective effect of piperine on benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice. Clinica Chimica Acta; International Journal of Clinical Chemistry, 350(1-2), 73–78. https://doi.org/10.1016/j.cccn.2004.07.004
   PubMed Web of Science ®Google Scholar
• Shabbir, M., Syed, D. N., Lall, R. K., Khan, M. R., & Mukhtar, H. (2015). Potent anti-proliferative, pro-apoptotic activity of the Maytenus royleanus extract against prostate cancer cells: Evidence in in-vitro and in-vivo models. PloS One, 10(3), e0119859. https://doi.org/10.1371/journal.pone.0119859
   PubMed Web of Science ®Google Scholar
• Shaikh, A. M., Shrivastava, B., Apte, K. G., & Navale, S. D. (2016). Medicinal plants as potential source of anticancer agents: A review. Journal of Pharmacognosy and Phytochemistry, 5(2), 291–295.
   Google Scholar
• Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 69(1), 7–34. https://doi.org/10.3322/caac.21551
   PubMed Web of Science ®Google Scholar
• Siegel, R., Naishadham, D., & Jemal, A. (2012). Cancer statistics for Hispanics/Latinos, 2012. CA: A Cancer Journal for Clinicians, 62(5), 283–298. https://doi.org/10.3322/caac.21153
   PubMed Web of Science ®Google Scholar
• Singh, M. P., Chauhan, A. K., & Kang, S. C. (2018). Morin hydrate ameliorates cisplatin-induced ER stress, inflammation and autophagy in HEK-293 cells and mice kidney via PARP-1 regulation. International Immunopharmacology, 56, 156–167. https://doi.org/10.1016/j.intimp.2018.01.031
   PubMed Web of Science ®Google Scholar
• Singh, S. P., Mishra, A., Shyanti, R. K., Singh, R. P., & Acharya, A. (2021). Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells. Biological Trace Element Research, 199(4), 1316–1331. https://doi.org/10.1007/s12011-020-02255-z
   PubMed Web of Science ®Google Scholar
• Song, M., Bode, A. M., Dong, Z., & Lee, M. H. (2019). AKT as a Therapeutic Target for Cancer. Cancer Research, 79(6), 1019–1031. https://doi.org/10.1158/0008-5472.CAN-18-2738
   PubMed Web of Science ®Google Scholar
• Subramaniyam, N., Arumugam, S., Ezthupurakkal, P. B., Ariraman, S., Biswas, I., Muthuvel, S. K., Balakrishnan, A., Alshammari, G. M., & Chinnasamy, T. (2018). Unveiling anticancer potential of glibenclamide: Its synergistic cytotoxicity with doxorubicin on cancer cells. Journal of Pharmaceutical and Biomedical Analysis, 154, 294–301. https://doi.org/10.1016/j.jpba.2018.03.025
   PubMed Web of Science ®Google Scholar
• Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (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), 209–249. https://doi.org/10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Tannock, I. F., de Wit, R., Berry, W. R., Horti, J., Pluzanska, A., Chi, K. N., Oudard, S., Théodore, C., James, N. D., Turesson, I., Rosenthal, M. A., & Eisenberger, M. A., & TAX 327 Investigators (2004). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. The New England Journal of Medicine, 351(15), 1502–1512. https://doi.org/10.1056/NEJMoa040720
   PubMed Web of Science ®Google Scholar
• Tawani, A., Amanullah, A., Mishra, A., & Kumar, A. (2016). Evidences for Piperine inhibiting cancer by targeting human G-quadruplex DNA sequences. Scientific Reports, 6, 39239. https://doi.org/10.1038/srep39239
   PubMed Web of Science ®Google Scholar
• Tuble, S. C., Anwar, J., & Gale, J. D. (2004). An approach to developing a force field for molecular simulation of martensitic phase transitions between phases with subtle differences in energy and structure. Journal of the American Chemical Society, 126(1), 396–405. https://doi.org/10.1021/ja0356131
   PubMed Web of Science ®Google Scholar
• Urbanowicz, R. A., Wang, R., Schiel, J. E., Keck, Z. Y., Kerzic, M. C., Lau, P., Rangarajan, S., Garagusi, K. J., Tan, L., Guest, J. D., Ball, J. K., Pierce, B. G., Mariuzza, R. A., Foung, S. K. H., & Fuerst, T. R. (2019). Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells. Journal of Virology, 93(7), e01403-18. https://doi.org/10.1128/JVI.01403-18
   PubMed Web of Science ®Google Scholar
• Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., & Mackerell, A. D., Jr (2010). CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry, 31(4), 671–690. https://doi.org/10.1002/jcc.21367
   PubMed Web of Science ®Google Scholar
• Wang, J., & Hou, T. (2012). Develop and test a solvent accessible surface area-based model in conformational entropy calculations. Journal of Chemical Information and Modeling, 52(5), 1199–1212. https://doi.org/10.1021/ci300064d
   PubMed Web of Science ®Google Scholar
• Yang, C., Ma, X., Wang, Z., Zeng, X., Hu, Z., Ye, Z., & Shen, G. (2017). Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation. Drug Design, Development and Therapy, 11, 431–439. https://doi.org/10.2147/DDDT.S126964
   PubMed Web of Science ®Google Scholar
• Yang, R., Suresh, S., & Velmurugan, R. (2022). Synthesis of Quinoline-2-Carboxylic Acid Aryl Ester and Its Apoptotic Action on PC3 Prostate Cancer Cell Line. Applied Biochemistry and Biotechnology, Advance online publication. https://doi.org/10.1007/s12010-022-04258-z
   Web of Science ®Google Scholar
• Yu, Y., Savage, R. E., Eathiraj, S., Meade, J., Wick, M. J., Hall, T., Abbadessa, G., & Schwartz, B. (2015). Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092. PloS One, 10(10), e0140479. https://doi.org/10.1371/journal.pone.0140479
   PubMed Web of Science ®Google Scholar
• Zheng, J., Zhou, Y., Li, Y., Xu, D. P., Li, S., & Li, H. B. (2016). Spices for Prevention and Treatment of Cancers. Nutrients, 8(8), 495. https://doi.org/10.3390/nu8080495
   PubMed Web of Science ®Google Scholar
• Zhou, H., Li, F., & Li, Y. (2022). Anti-Cancer Activity of Gedunin by Induction of Apoptosis in Human Gastric Cancer AGS Cells. Applied Biochemistry and Biotechnology, 194(11), 5322–5332. https://doi.org/10.1007/s12010-022-04001-8
   PubMed Web of Science ®Google Scholar