Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Computational Techniques
2.1.1. Docking of Withaferin-A, Withanone, and YM-155 with Survivin
2.1.2. All-Atom Molecular Dynamics Simulations of the Ligand–Survivin Complex
2.1.3. Analyzing the Simulation Trajectory
2.1.4. MM/GBSA Binding Free Energy
2.2. Experimental Techniques
2.2.1. Cell Culture and Treatments
2.2.2. HPLC Analysis
2.2.3. Cell Viability Assay
2.2.4. Morphological Observations
2.2.5. Colony Formation Assay
2.2.6. Flow Cytometry Analysis
2.2.7. Apoptosis Assay
2.2.8. Western Blotting
2.2.9. Immunocytochemistry
2.2.10. RNA Extraction and Quantitative Real-Time Polymerase Chain Reaction
2.2.11. Wound Scratch Assay
2.2.12. Cell Invasion Assay
2.2.13. Statistical Analysis
3. Results
3.1. Withaferin-A Showed Good Docking to the Survivin Homodimer
3.2. Downregulation of Survivin Protein and mRNA by Wi-A-Rich Extract of Ashwagandha Leaves (Wi-AREAL)
3.3. Wi-AREAL-Treated Cells Showed G2 Growth Arrest and Apoptosis
3.4. Low Nontoxic Doses of Wi-AREAL Showed Anti-Metastasis Potential
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Albadari, N.; Li, W. Survivin Small Molecules Inhibitors: Recent Advances and Challenges. Molecules 2023, 28, 1376. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Duan, N.; Zhang, C.; Zhang, W. Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies. J. Cancer 2016, 7, 314–323. [Google Scholar] [CrossRef] [PubMed]
- Tamm, I.; Wang, Y.; Sausville, E.; Scudiero, D.A.; Vigna, N.; Oltersdorf, T.; Reed, J.C. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 1998, 58, 5315–5320. [Google Scholar] [PubMed]
- Li, F.; Ambrosini, G.; Chu, E.Y.; Plescia, J.; Tognin, S.; Marchisio, P.C.; Altieri, D.C. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998, 396, 580–584. [Google Scholar] [CrossRef]
- Dohi, T.; Beltrami, E.; Wall, N.R.; Plescia, J.; Altieri, D.C. Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J. Clin. Investig. 2004, 114, 1117–1127. [Google Scholar] [CrossRef]
- Foster, P.A.; Ho, Y.T.; Newman, S.P.; Leese, M.P.; Potter, B.V.; Reed, M.J.; Purohit, A. STX140 and STX641 cause apoptosis via the intrinsic mitochondrial pathway and down-regulate survivin and XIAP expression in ovarian and prostate cancer cells. Anticancer Res. 2009, 29, 3751–3757. [Google Scholar]
- Wang, Z.; Li, Y.; Liu, M.; Chen, D.; Lu, J.; Ji, Y.; Xing, Z.; Wang, Y. 3BDO inhibits the proliferation, epithelial-mesenchymal transition (EMT), and stemness via suppressing survivin in human glioblastoma cells. J. Cancer 2022, 13, 1203–1213. [Google Scholar] [CrossRef]
- Warrier, N.M.; Krishnan, R.K.; Prabhu, V.; Hariharapura, R.C.; Agarwal, P.; Kumar, P. Survivin Inhibition by Piperine Sensitizes Glioblastoma Cancer Stem Cells and Leads to Better Drug Response. Int. J. Mol. Sci. 2022, 23, 7604. [Google Scholar] [CrossRef]
- Frassanito, M.A.; Saltarella, I.; Vinella, A.; Muzio, L.L.; Pannone, G.; Fumarulo, R.; Vacca, A.; Mariggio, M.A. Survivin overexpression in head and neck squamous cell carcinomas as a new therapeutic target (Review). Oncol. Rep. 2019, 41, 2615–2624. [Google Scholar] [CrossRef]
- Zhang, M.; Yang, J.; Li, F. Transcriptional and post-transcriptional controls of survivin in cancer cells: Novel approaches for cancer treatment. J. Exp. Clin. Cancer Res. 2006, 25, 391–402. [Google Scholar]
- Li, F.; Aljahdali, I.; Ling, X. Cancer therapeutics using survivin BIRC5 as a target: What can we do after over two decades of study? J. Exp. Clin. Cancer Res. 2019, 38, 368. [Google Scholar] [CrossRef]
- Asraf, H.; Avunie-Masala, R.; Hershfinkel, M.; Gheber, L. Mitotic slippage and expression of survivin are linked to differential sensitivity of human cancer cell-lines to the Kinesin-5 inhibitor monastrol. PLoS ONE 2015, 10, e0129255. [Google Scholar] [CrossRef] [PubMed]
- George, R.; Hehlgans, S.; Fleischmann, M.; Rodel, C.; Fokas, E.; Rodel, F. Advances in nanotechnology-based platforms for survivin-targeted drug discovery. Expert Opin. Drug Discov. 2022, 17, 733–754. [Google Scholar] [CrossRef] [PubMed]
- Dong, Z.; Yang, L.; Lai, D. KLF5 strengthens drug resistance of ovarian cancer stem-like cells by regulating survivin expression. Cell Prolif. 2013, 46, 425–435. [Google Scholar] [CrossRef]
- Noh, E.J.; Lim, D.S.; Jeong, G.; Lee, J.S. An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner. Biochem. Biophys. Res. Commun. 2009, 378, 326–331. [Google Scholar] [CrossRef]
- Cornago, M.; Garcia-Alberich, C.; Blasco-Angulo, N.; Vall-Llaura, N.; Nager, M.; Herreros, J.; Comella, J.X.; Sanchis, D.; Llovera, M. Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe. Cell Death Dis. 2014, 5, e1435. [Google Scholar] [CrossRef]
- Jiang, L.; Luo, R.Y.; Yang, J.; Cheng, Y.X. Knockdown of survivin contributes to antitumor activity in cisplatin-resistant ovarian cancer cells. Mol. Med. Rep. 2013, 7, 425–430. [Google Scholar] [CrossRef]
- Togashi, K.; Okada, M.; Yamamoto, M.; Suzuki, S.; Sanomachi, T.; Seino, S.; Yamashita, H.; Kitanaka, C. A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel. Anticancer Res. 2018, 38, 4535–4542. [Google Scholar] [CrossRef] [PubMed]
- Zhao, G.; Wang, Q.; Gu, Q.; Qiang, W.; Wei, J.J.; Dong, P.; Watari, H.; Li, W.; Yue, J. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells. Oncotarget 2017, 8, 94666–94680. [Google Scholar] [CrossRef]
- Peery, R.; Cui, Q.; Kyei-Baffour, K.; Josephraj, S.; Huang, C.; Dong, Z.; Dai, M.; Zhang, J.T.; Liu, J.Y. A novel survivin dimerization inhibitor without a labile hydrazone linker induces spontaneous apoptosis and synergizes with docetaxel in prostate cancer cells. Bioorg. Med. Chem. 2022, 65, 116761. [Google Scholar] [CrossRef]
- Nakahara, T.; Kita, A.; Yamanaka, K.; Mori, M.; Amino, N.; Takeuchi, M.; Tominaga, F.; Hatakeyama, S.; Kinoyama, I.; Matsuhisa, A.; et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007, 67, 8014–8021. [Google Scholar] [CrossRef] [PubMed]
- Iwasa, T.; Okamoto, I.; Suzuki, M.; Nakahara, T.; Yamanaka, K.; Hatashita, E.; Yamada, Y.; Fukuoka, M.; Ono, K.; Nakagawa, K. Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin. Cancer Res. 2008, 14, 6496–6504. [Google Scholar] [CrossRef] [PubMed]
- Yamanaka, K.; Nakata, M.; Kaneko, N.; Fushiki, H.; Kita, A.; Nakahara, T.; Koutoku, H.; Sasamata, M. YM155, a selective survivin suppressant, inhibits tumor spread and prolongs survival in a spontaneous metastatic model of human triple negative breast cancer. Int. J. Oncol. 2011, 39, 569–575. [Google Scholar] [CrossRef]
- Nakahara, T.; Kita, A.; Yamanaka, K.; Mori, M.; Amino, N.; Takeuchi, M.; Tominaga, F.; Kinoyama, I.; Matsuhisa, A.; Kudou, M.; et al. Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci. 2011, 102, 614–621. [Google Scholar] [CrossRef]
- Minoda, M.; Kawamoto, T.; Ueha, T.; Kamata, E.; Morishita, M.; Harada, R.; Toda, M.; Onishi, Y.; Hara, H.; Kurosaka, M.; et al. Antitumor effect of YM155, a novel small-molecule survivin suppressant, via mitochondrial apoptosis in human MFH/UPS. Int. J. Oncol. 2015, 47, 891–899. [Google Scholar] [CrossRef]
- Yoon, D.H.; Shin, J.S.; Jin, D.H.; Hong, S.W.; Jung, K.A.; Kim, S.M.; Hong, Y.S.; Kim, K.P.; Lee, J.L.; Suh, C.; et al. The survivin suppressant YM155 potentiates chemosensitivity to gemcitabine in the human pancreatic cancer cell line MiaPaCa-2. Anticancer Res. 2012, 32, 1681–1688. [Google Scholar]
- Hong, M.; Ren, M.Q.; Silva, J.; Paul, A.; Wilson, W.D.; Schroeder, C.; Weinberger, P.; Janik, J.; Hao, Z. YM155 inhibits topoisomerase function. Anticancer Drugs 2017, 28, 142–152. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Ke, W.; Zhao, X.; Lu, Z. Resina Draconis extract exerts anti-HCC effects through METTL3-m6A-Survivin axis. Phytother. Res. 2022, 36, 2542–2557. [Google Scholar] [CrossRef]
- Hahm, E.R.; Singh, S.V. Withaferin A-induced apoptosis in human breast cancer cells is associated with suppression of inhibitor of apoptosis family protein expression. Cancer Lett. 2013, 334, 101–108. [Google Scholar] [CrossRef]
- Um, H.J.; Min, K.J.; Kim, D.E.; Kwon, T.K. Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells. Biochem. Biophys. Res. Commun. 2012, 427, 24–29. [Google Scholar] [CrossRef]
- Kaul, S.C.K.; Wadhwa, R. Science of Ashwagandha: Preventive and Therapeutic Potentials; Springer: Cham, Switzerland, 2017. [Google Scholar]
- Yu, Y.; Wang, J.; Kaul, S.C.; Wadhwa, R.; Miyako, E. Folic Acid Receptor-Mediated Targeting Enhances the Cytotoxicity, Efficacy, and Selectivity of Withania somnifera Leaf Extract: In vitro and in vivo Evidence. Front. Oncol. 2019, 9, 602. [Google Scholar] [CrossRef] [PubMed]
- Sundar, D.; Yu, Y.; Katiyar, S.P.; Putri, J.F.; Dhanjal, J.K.; Wang, J.; Sari, A.N.; Kolettas, E.; Kaul, S.C.; Wadhwa, R. Wild type p53 function in p53(Y220C) mutant harboring cells by treatment with Ashwagandha derived anticancer withanolides: Bioinformatics and experimental evidence. J. Exp. Clin. Cancer Res. 2019, 38, 103. [Google Scholar] [CrossRef]
- Kumar, P.; Sharma, R.; Garg, N. Withania somnifera—A magic plant targeting multiple pathways in cancer related inflammation. Phytomedicine 2022, 101, 154137. [Google Scholar] [CrossRef] [PubMed]
- Hahm, E.R.; Kim, S.H.; Singh, K.B.; Singh, K.; Singh, S.V. A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer. Cancer Prev. Res. 2020, 13, 721–734. [Google Scholar] [CrossRef]
- Yu, Y.; Katiyar, S.P.; Sundar, D.; Kaul, Z.; Miyako, E.; Zhang, Z.; Kaul, S.C.; Reddel, R.R.; Wadhwa, R. Withaferin-A kills cancer cells with and without telomerase: Chemical, computational and experimental evidences. Cell Death Dis. 2017, 8, e2755. [Google Scholar] [CrossRef]
- Tewari, D.; Chander, V.; Dhyani, A.; Sahu, S.; Gupta, P.; Patni, P.; Kalick, L.S.; Bishayee, A. Withania somnifera (L.) Dunal: Phytochemistry, structure-activity relationship, and anticancer potential. Phytomedicine 2022, 98, 153949. [Google Scholar] [CrossRef]
- Atteeq, M. Evaluating anticancer properties of Withaferin A-a potent phytochemical. Front. Pharmacol. 2022, 13, 975320. [Google Scholar] [CrossRef] [PubMed]
- Wadegaonkar, V.P.; Wadegaonkar, P.A. Withanone as an inhibitor of survivin: A potential drug candidate for cancer therapy. J. Biotechnol. 2013, 168, 229–233. [Google Scholar] [CrossRef]
- Zhou, J.; Guo, X.; Chen, W.; Wang, L.; Jin, Y. Targeting survivin sensitizes cervical cancer cells to radiation treatment. Bioengineered 2020, 11, 130–140. [Google Scholar] [CrossRef] [PubMed]
- Chang, Y.C.; Shieh, M.C.; Chang, Y.H.; Huang, W.L.; Su, W.C.; Cheng, F.Y.; Cheung, C.H.A. Development of a cancer cells self-activating and miR-125a-5p expressing poly-pharmacological nanodrug for cancer treatment. Int. J. Mol. Med. 2022, 50, 102. [Google Scholar] [CrossRef]
- Du, J.; Kelly, A.E.; Funabiki, H.; Patel, D.J. Structural basis for recognition of H3T3ph and Smac/DIABLO N-terminal peptides by human Survivin. Structure 2012, 20, 185–195. [Google Scholar] [CrossRef] [PubMed]
- Protein Preparation Wizard; Epik, Impact, Prime, LigPrep, Glide, Schrödinger, LLC: New York, NY, USA; Desmond Molecular Dynamics System, D.E. Shaw Research: New York, NY, USA, 2020.
- Chantalat, L.; Skoufias, D.A.; Kleman, J.P.; Jung, B.; Dideberg, O.; Margolis, R.L. Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions. Mol. Cell 2000, 6, 183–189. [Google Scholar] [CrossRef]
- Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 2006, 49, 6177–6196. [Google Scholar] [CrossRef]
- Schrödinger. Schrödinger Release 2020-1: Maestro 019-3 SR G, LigPrep, Protein Preparation Wizard, Prime, Desmond Molecular Dynamics System, Maestro-Desmond Interoperability Tools; Schrödinger, LLC.: New York, NY, USA, 2020. [Google Scholar]
- Bowers, K.J.; Chow, D.E.; Xu, H.; Dror, R.O.; Eastwood, M.P.; Gregersen, B.A.; Klepeis, J.L.; Kolossvary, I.; Moraes, M.A.; Sacerdoti, F.D. Scalable algorithms for molecular dynamics simulations on commodity clusters. In SC’06: Proceedings of the 2006 ACM/IEEE Conference on Supercomputing; IEEE: New York, NY, USA, 2006; p. 43. [Google Scholar]
- Harder, E.; Damm, W.; Maple, J.; Wu, C.; Reboul, M.; Xiang, J.Y.; Wang, L.; Lupyan, D.; Dahlgren, M.K.; Knight, J.L. OPLS3: A force field providing broad coverage of drug-like small molecules and proteins. J. Chem. Theory Comput. 2016, 12, 281–296. [Google Scholar] [CrossRef]
- Liu, K.; Kokubo, H. Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations: A cross-docking study. J. Chem. Inf. Model. 2017, 57, 2514–2522. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Abel, R.; Zhu, K.; Cao, Y.; Zhao, S.; Friesner, R.A. The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling. Proteins Struct. Funct. Bioinform. 2011, 79, 2794–2812. [Google Scholar] [CrossRef] [PubMed]
- Genheden, S.; Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov. 2015, 10, 449–461. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Zhang, H.; Kaul, A.; Li, K.; Priyandoko, D.; Kaul, S.C.; Wadhwa, R. Effect of Ashwagandha Withanolides on Muscle Cell Differentiation. Biomolecules 2021, 11, 1454. [Google Scholar] [CrossRef]
- Marioni, G.; D’Alessandro, E.; Bertolin, A.; Staffieri, A. Survivin multifaceted activity in head and neck carcinoma: Current evidence and future therapeutic challenges. Acta Otolaryngol. 2010, 130, 4–9. [Google Scholar] [CrossRef]
- Kondapuram, S.K.; Ramachandran, H.K.; Arya, H.; Coumar, M.S. Targeting survivin for cancer therapy: Strategies, small molecule inhibitors and vaccine-based therapeutics in development. Life Sci. 2023, 335, 122260–122279. [Google Scholar] [CrossRef]
- Tazawa, H.; Shigeyasu, K.; Noma, K.; Kagawa, S.; Sakurai, F.; Mizuguchi, H.; Kobayashi, H.; Imamura, T.; Fujiwara, T. Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment. Cancer Sci. 2022, 113, 1919–1929. [Google Scholar] [CrossRef] [PubMed]
- Mirza, A.; McGuirk, M.; Hockenberry, T.N.; Wu, Q.; Ashar, H.; Black, S.; Wen, S.F.; Wang, L.; Kirschmeier, P.; Bishop, W.R.; et al. Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene 2002, 21, 2613–2622. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Lyu, H.; Wang, J.; Liu, B. MicroRNA regulation and therapeutic targeting of survivin in cancer. Am. J. Cancer Res. 2014, 5, 20–31. [Google Scholar] [PubMed]
- Voges, Y.; Michaelis, M.; Rothweiler, F.; Schaller, T.; Schneider, C.; Politt, K.; Mernberger, M.; Nist, A.; Stiewe, T.; Wass, M.N.; et al. Effects of YM155 on survivin levels and viability in neuroblastoma cells with acquired drug resistance. Cell Death Dis. 2016, 7, e2410. [Google Scholar] [CrossRef]
- Sari, A.N.; Bhargava, P.; Dhanjal, J.K.; Putri, J.F.; Radhakrishnan, N.; Shefrin, S.; Ishida, Y.; Terao, K.; Sundar, D.; Kaul, S.C.; et al. Combination of Withaferin-A and CAPE Provides Superior Anticancer Potency: Bioinformatics and Experimental Evidence to Their Molecular Targets and Mechanism of Action. Cancers 2020, 12, 1160. [Google Scholar] [CrossRef]
- Bhargava, P.; Malik, V.; Liu, Y.; Ryu, J.; Kaul, S.C.; Sundar, D.; Wadhwa, R. Molecular Insights Into Withaferin-A-Induced Senescence: Bioinformatics and Experimental Evidence to the Role of NFkappaB and CARF. J. Gerontol. A Biol. Sci. Med. Sci. 2019, 74, 183–191. [Google Scholar] [CrossRef] [PubMed]
- Suman, S.; Das, T.P.; Sirimulla, S.; Alatassi, H.; Ankem, M.K.; Damodaran, C. Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells. Oncotarget 2016, 7, 13854–13864. [Google Scholar] [CrossRef]
- Thaiparambil, J.T.; Bender, L.; Ganesh, T.; Kline, E.; Patel, P.; Liu, Y.; Tighiouart, M.; Vertino, P.M.; Harvey, R.D.; Garcia, A.; et al. Withaferin A inhibits breast cancer invasion and metastasis at sub-cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation. Int. J. Cancer 2011, 129, 2744–2755. [Google Scholar] [CrossRef]
- Garg, H.; Suri, P.; Gupta, J.C.; Talwar, G.P.; Dubey, S. Survivin: A unique target for tumor therapy. Cancer Cell Int. 2016, 16, 49–64. [Google Scholar] [CrossRef] [PubMed]
- Pachimatla, A.G.; Fenstermaker, R.; Ciesielski, M.; Yendamuri, S. Survivin in lung cancer: A potential target for therapy and prevention-a narrative review. Transl Lung Cancer Res. 2024, 13, 362–374. [Google Scholar] [CrossRef]
- Sim, M.Y.; Yuen, J.S.P.; Go, M.L. Anti-survivin effect of the small molecule inhibitor YM155 in RCC cells is mediated by time-dependent inhibition of the NF-κB pathway. Sci. Rep. 2018, 8, 10289–10298. [Google Scholar] [CrossRef]
- Sultana, T.; Okla, M.K.; Ahmed, M.; Akhtar, N.; Al-Hashimi, A.; Abdelgawad, H.; Haq, I. Withaferin A: From Ancient Remedy to Potential Drug Candidate. Molecules 2021, 26, 7696. [Google Scholar] [CrossRef] [PubMed]
- Xing, Z.; Su, A.; Mi, L.; Zhang, Y.; He, T.; Qiu, Y.; Wei, T.; Li, Z.; Zhu, J.; Wu, W. Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment—Pharmacology and Mechanisms. Drug Des. Dev. Ther. 2023, 17, 2909–2929. [Google Scholar] [CrossRef]
- Cui, Q.; Huang, C.; Liu, J.Y.; Zhang, J.T. Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective. J. Med. Chem. 2023, 66, 16515–16545. [Google Scholar] [CrossRef]
- Kalra, R.S.; Chaudhary, A.; Omar, A.; Li, X.; Khurana, M.; Kaul, S.C.; Wadhwa, R. Stress-induced changes in CARF expression serve as a quantitative predictive measure of cell proliferation fate. Exp. Cell Res. 2023, 429, 113669. [Google Scholar] [CrossRef] [PubMed]
- Shiota, M.; Ikeda, Y.; Kaul, Z.; Itadani, J.; Kaul, S.C.; Wadhwa, R. Internalizing antibody-based targeted gene delivery for human cancer cells. Hum. Gene Ther. 2007, 18, 1153–1160. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wadhwa, R.; Wang, J.; Shefrin, S.; Zhang, H.; Sundar, D.; Kaul, S.C. Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling. Cancers 2024, 16, 3090. https://doi.org/10.3390/cancers16173090
Wadhwa R, Wang J, Shefrin S, Zhang H, Sundar D, Kaul SC. Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling. Cancers. 2024; 16(17):3090. https://doi.org/10.3390/cancers16173090
Chicago/Turabian StyleWadhwa, Renu, Jia Wang, Seyad Shefrin, Huayue Zhang, Durai Sundar, and Sunil C. Kaul. 2024. "Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling" Cancers 16, no. 17: 3090. https://doi.org/10.3390/cancers16173090