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New Frontiers in Promoting TRAIL-Mediated Cell Death: Focus on Natural Sensitizers, miRNAs, and Nanotechnological Advancements

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Abstract

Cancer is a multifaceted and genomically complex disease, and rapidly emerging scientific evidence is emphasizing on intra-tumor heterogeneity within subpopulations of tumor cells and rapidly developing resistance against different molecular therapeutics. There is an overwhelmingly increasing list of agents currently being tested for efficacy against cancer. In accordance with the concept that therapeutic agents must have fewer off target effects and considerable efficacy, TRAIL has emerged as one among the most deeply investigated proteins reportedly involved in differential killing of tumor cells. Considerable killing activity of TRAIL against different cancers advocated its entry into clinical trials. However, data obtained through preclinical and cell culture studies are deepening our understanding of wide-ranging mechanisms which induce resistance against TRAIL-based therapeutics. These include downregulation of death receptors, overexpression of oncogenes, inactivation of tumor suppressor genes, imbalance of pro- and anti-apoptotic proteins, and inactivation of intrinsic and extrinsic pathways. Substantial fraction of information has been added into existing pool of knowledge related to TRAIL biology and recently accumulating evidence is adding new layers to regulation of TRAIL-induced apoptosis. Certain hints have emerged underscoring miR135a-3p- and miR-143-mediated regulation of TRAIL-induced apoptosis, and natural agents have shown remarkable efficacy in improving TRAIL-based therapeutics by increasing expression of tumor suppressor miRNAs. In this review, we summarize most recent breakthroughs related to naturopathy and strategies to nanotechnologically deliver TRAIL to the target site in xenografted mice. We also set spotlight on positive and negative regulators of TRAIL-mediated signaling. Comprehensive knowledge of genetics and proteomics of TRAIL-based signaling network obtained from cancer patients of different populations will be helpful in getting a step closer to personalized medicine.

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References

  1. Hylander, B. L., Sen, A., Beachy, S. H., Pitoniak, R., Ullas, S., Gibbs, J. F., et al. (2015). Tumor priming by Apo2L/TRAIL reduces interstitial fluid pressure and enhances efficacy of liposomal gemcitabine in a patient derived xenograft tumor model. Journal of Control Release, 217, 160–169.

    Article  CAS  Google Scholar 

  2. He, X., Chen, X., Zhang, X., Duan, X., Pan, T., Hu, Q., et al. (2015). An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes. Nucleic Acids Research, 43(7), 3712–3725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Li, T., Su, L., Lei, Y., Liu, X., Zhang, Y., & Liu, X. (2015). DDIT3 and KAT2A proteins regulate TNFRSF10A and TNFRSF10B expression in endoplasmic reticulum stress-mediated apoptosis in human lung cancer cells. Journal of Biological Chemistry, 290(17), 11108–11118.

    Article  CAS  PubMed  Google Scholar 

  4. Oh, Y. T., Deng, J., Yue, P., Owonikoko, T. K., Khuri, F. R., & Sun, S. Y. (2015). Inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs response of cancer cells to DR5-mediated apoptosis and T cell-induced killing. Oncogene,. doi:10.1038/onc.2015.97.

    Google Scholar 

  5. Yanagi, T., Shi, R., Aza-Blanc, P., Reed, J. C., & Matsuzawa, S. (2015). PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines. PLoS ONE, 10(3), e0119404.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Xu, J., Zhou, J. Y., Xu, Z., Kho, D. H., Zhuang, Z., Raz, A., & Wu, G. S. (2014). The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling. Cell Cycle, 13(23), 3750–3758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lin, C. M., Ma, J. M., Zhang, L., Hao, Z. Y., Zhou, J., Zhou, Z. Y., et al. (2015). Inhibition of transient receptor potential melastain 7 enhances apoptosis induced by TRAIL in PC-3 cells. Asian Pacific Journal of Cancer Prevention, 16(10), 4469–4475.

    Article  PubMed  Google Scholar 

  8. Lin, J. Y., Ke, Y. M., Lai, J. S., & Ho, T. F. (2015). Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells. Phytomedicine, 22(10), 929–938.

    Article  CAS  PubMed  Google Scholar 

  9. Raimondo, S., Naselli, F., Fontana, S., Monteleone, F., Lo Dico, A., Saieva, L., et al. (2015). Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 6(23), 19514–19527.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yoon, J. Y., Cho, H. S., Lee, J. J., Lee, H. J., Jun, S. Y., Lee, J. H., et al. (2015). Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells. Molecular Carcinogenesis,. doi:10.1002/mc.22288.

    Google Scholar 

  11. Philipp, S., Sosna, J., Plenge, J., Kalthoff, H., & Adam, D. (2015). Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis. Cell Communication Signal, 13, 25.

    Article  Google Scholar 

  12. Jeong, J. W., Lee, W. S., Go, S. I., Nagappan, A., Baek, J. Y., Lee, J. D., et al. (2015). Pachymic acid induces apoptosis of EJ bladder cancer cells by DR5 up-regulation, ROS generation, modulation of Bcl-2 and IAP family members. Phytotherapy Research,. doi:10.1002/ptr.5402.

    Google Scholar 

  13. Kumazaki, M., Shinohara, H., Taniguchi, K., Ueda, H., Nishi, M., Ryo, A., & Akao, Y. (2015). Understanding of tolerance in TRAIL-induced apoptosis and cancelation of its machinery by α-mangostin, a xanthone derivative. Oncotarget, 1, 1–2.

    Google Scholar 

  14. Huang, H., Chen, A. Y., Ye, X., Li, B., Rojanasakul, Y., Rankin, G. O., & Chen, Y. C. (2015). Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway. International Journal of Oncology,. doi:10.3892/ijo.2015.3133.

    Google Scholar 

  15. Huang, K., Duan, N., Zou, W., Zhang, C., Lai, Y., & Shen, P. (2015). Hua Z Fused hydrophobic elastin-like-peptides (ELP) enhance biological activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Protein and Peptide Letters, 1, 1–2.

    Google Scholar 

  16. Chang, C. C., Kuan, C. P., Lin, J. Y., Lai, J. S., & Ho, T. F. (2015). Tanshinone IIA facilitates TRAIL sensitization by up-regulating DR5 through the ROS-JNK-CHOP signaling axis in human ovarian carcinoma cell lines. Chemical Research in Toxicology, 28(8), 1574–1583.

    Article  CAS  PubMed  Google Scholar 

  17. Minker, C., Duban, L., Karas, D., Järvinen, P., Lobstein, A., & Muller, C. D. (2015). Impact of procyanidins from different berries on caspase 8 activation in colon cancer. Oxidative Medicine and Cellular Longevity, 2015, 154164.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ye, Y., Miao, S., Wang, Y., Zhou, J., & Lu, R. (2015). 3,3′-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells. Oncology Letters, 9(5), 2393–2397.

    PubMed  PubMed Central  Google Scholar 

  19. Shin, D., Kwon, H. Y., Sohn, E. J., Nam, M. S., Kim, J. H., Lee, J. C., et al. (2015). Upregulation of death receptor 5 and production of reactive oxygen species mediate sensitization of PC-3 prostate cancer cells to TRAIL induced apoptosis by vitisin A. Cellular Physiology and Biochemistry, 36(3), 1151–1162.

    Article  CAS  PubMed  Google Scholar 

  20. Karmakar, U. K., Ishikawa, N., Toume, K., Arai, M. A., Sadhu, S. K., Ahmed, F., & Ishibashi, M. (2015). Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium. Bioorganic & Medicinal Chemistry, 23(15), 4746–4754.

    Article  CAS  Google Scholar 

  21. Henrich, C. J., Brooks, A. D., Erickson, K. L., Thomas, C. L., Bokesch, H. R., Tewary, P., et al. (2015). Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation. Cell Death and Disease, 6, e1666. doi:10.1038/cddis.2015.38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fuentes, R. G., Toume, K., Arai, M. A., Sadhu, S. K., Ahmed, F., & Ishibashi, M. (2015). Scopadulciol, isolated from Scoparia dulcis, Induces β-catenin degradation and overcomes tumor necrosis factor-related apoptosis ligand resistance in AGS human gastric adenocarcinoma cells. Journal of Natural Products, 78(4), 864–872.

    Article  CAS  PubMed  Google Scholar 

  23. Joshi, P., Jeon, Y. J., Laganà, A., Middleton, J., Secchiero, P., Garofalo, M., & Croce, C. M. (2015). MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proceedings of the National Academy of Sciences USA, 112(28), 8650–8655.

    Article  CAS  Google Scholar 

  24. Jeon, Y. J., Middleton, J., Kim, T., Laganà, A., Piovan, C., Secchiero, P., et al. (2015). A set of NF-κB-regulated microRNAs induces acquired TRAIL resistance in lung cancer. Proceedings of the National Academy of Sciences USA, 112(26), E3355–E3364.

    Article  CAS  Google Scholar 

  25. Kumazaki, M., Shinohara, H., Taniguchi, K., Yamada, N., Ohta, S., Ichihara, K., & Akao, Y. (2014). Propolis cinnamic acid derivatives induce apoptosis through both extrinsic and intrinsic apoptosis signaling pathways and modulate of miRNA expression. Phytomedicine, 21(8–9), 1070–1077.

    Article  CAS  PubMed  Google Scholar 

  26. Shin, E. A., Sohn, E. J., Won, G., Choi, J. U., Jeong, M., Kim, B., et al. (2014). Upregulation of microRNA135a-3p and death receptor 5 plays a critical role in Tanshinone I sensitized prostate cancer cells to TRAIL induced apoptosis. Oncotarget, 5(14), 5624–5636.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Braun, F. K., Mathur, R., Sehgal, L., Wilkie-Grantham, R., Chandra, J., Berkova, Z., & Samaniego, F. (2015). Inhibition of methyltransferases accelerates degradation of cFLIP and sensitizes B-cell lymphoma cells to TRAIL-induced apoptosis. PLoS ONE, 10(3), e0117994.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wang, Y., Santos, A., Kaur, G., Evdokiou, A., & Losic, D. (2014). Structurally engineered anodic alumina nanotubes as nano-carriers for delivery of anticancer therapeutics. Biomaterials, 35(21), 5517–5526.

    Article  CAS  PubMed  Google Scholar 

  29. Zakaria, A. B., Picaud, F., Rattier, T., Pudlo, M., Saviot, L., Chassagnon, R., et al. (2015). Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing. Nano Letters, 15(2), 891–895.

    Article  CAS  PubMed  Google Scholar 

  30. Chen, Z., Zhang, L., He, Y., & Li, Y. (2014). Sandwich-type Au-PEI/DNA/PEI-Dexa nanocomplex for nucleus-targeted gene delivery in vitro and in vivo. ACS Applied Materials Interfaces, 6(16), 14196–14206.

    Article  CAS  PubMed  Google Scholar 

  31. Min, S. Y., Byeon, H. J., Lee, C. K., Seo, J., Lee, E. S., Shin, B. S., et al. (2015). Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer. International Journal of Pharmaceutics, 1, 1–2.

    Google Scholar 

  32. Wang, X., Tai, Z., Tian, J., Zhang, W., Yao, C., Zhang, L., et al. (2015). Reducible chimeric polypeptide consisting of octa-d-arginine and tetra-l-histidine peptides as an efficient gene delivery vector. International Journal of Nanomedicine, 10, 4669–4690.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim, I., Choi, J. S., Lee, S., Byeon, H. J., Lee, E. S., Shin, B. S., et al. (2015). In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein. Journal of Control Release, 214, 30–39.

    Article  CAS  Google Scholar 

  34. Kim, M. J., Kwon, S. B., Ham, S. H., Jeong, E. S., Choi, Y. K., Choi, K. D., et al. (2015). H9 inhibits tumor growth and induces apoptosis via intrinsic and extrinsic signaling pathway in human non-small cell lung cancer xenografts. Journal of Microbiology and Biotechnology, 25(5), 648–657.

    CAS  PubMed  Google Scholar 

  35. Miao, L., Liu, C., Ge, J., Yang, W., Liu, J., Sun, W., et al. (2014). Antitumor effect of TRAIL on oral squamous cell carcinoma using magnetic nanoparticle-mediated gene expression. Cell Biochemistry and Biophysics, 69(3), 663–672.

    Article  CAS  PubMed  Google Scholar 

  36. Ren, H., Zhou, L., Liu, M., Lu, W., & Gao, C. (2015). Peptide GE11-Polyethylene Glycol-Polyethylenimine for targeted gene delivery in laryngeal cancer. Medical Oncology, 32(7), 185.

    Article  PubMed  Google Scholar 

  37. Ediriwickrema, A., Zhou, J., Deng, Y., & Saltzman, W. M. (2014). Multi-layered nanoparticles for combination gene and drug delivery to tumors. Biomaterials, 35(34), 9343–9354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zheng, Y., Chen, H., Zeng, X., Liu, Z., Xiao, X., Zhu, Y., et al. (2013). Surface modification of TPGS-b-(PCL-ran-PGA) nanoparticles with polyethyleneimine as a co-delivery system of TRAIL and endostatin for cervical cancer gene therapy. Nanoscale Research Letters, 8(1), 161.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Riehle, R. D., Cornea, S., Degterev, A., & Torchilin, V. (2013). Micellar formulations of pro-apoptotic DM-PIT-1 analogs and TRAIL in vitro and in vivo. Drug Deliv., 20(2), 78–85.

    Article  CAS  PubMed  Google Scholar 

  40. Bae, S., Ma, K., Kim, T. H., Lee, E. S., Oh, K. T., Park, E. S., et al. (2012). Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosis-inducing ligand and transferrin for targeting multiple tumor types. Biomaterials, 33(5), 1536–1546.

    Article  CAS  PubMed  Google Scholar 

  41. Hwang, J. S., Lee, H. C., Oh, S. C., Lee, D. H., & Kwon, K. H. (2015). Shogaol overcomes TRAIL resistance in colon cancer cells via inhibiting of survivin. Tumour Biology, 1, 1–2.

    Google Scholar 

  42. Yang, P., Tuo, L., Wu, Q., & Cao, X. (2014). Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP. Hepato-Gastroenterology, 61(133), 1229–1234.

    CAS  Google Scholar 

  43. Trivedi, R., Maurya, R., & Mishra, D. P. (2014). Medicarpin, a legume phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the induction of DR5 and activation of the ROS-JNK-CHOP pathway. Cell Death and Disease, 5, e1465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhang, Z., Li, Z., Wu, X., Zhang, C. F., Calway, T., He, T. C., et al. (2015). TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol. Journal of Pharmacological Sciences, 127(1), 83–91.

    Article  CAS  PubMed  Google Scholar 

  45. Yim, N. H., Jung, Y. P., Kim, A., Kim, T., & Ma, J. Y. (2015). Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncology Reports, 34(2), 1058–1064.

    PubMed  Google Scholar 

  46. Tse, A. K., Chow, K. Y., Cao, H. H., Cheng, C. Y., Kwan, H. Y., Yu, H., et al. (2013). The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand. Journal of Biological Chemistry, 288(41), 29923–29933.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Fatima, A., Abdul, A. B., Abdullah, R., Karjiban, R. A., & Lee, V. S. (2015). Binding mode analysis of zerumbone to key signal proteins in the tumor necrosis factor pathway. International Journal of Molecular Sciences, 16(2), 2747–2766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lee, J. H., Cho, H. D., Jeong, I. Y., Lee, M. K., & Seo, K. I. (2014). Sensitization of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant primary prostate cancer cells by isoegomaketone from Perilla frutescens. Journal of Natural Products, 77(11), 2438–2443.

    Article  CAS  PubMed  Google Scholar 

  49. Chou, Y. C., Chang, M. Y., Wang, M. J., Harnod, T., Hung, C. H., Lee, H. T., et al. (2015). PEITC induces apoptosis of Human Brain Glioblastoma GBM8401 Cells through the extrinsic- and intrinsic -signaling pathways. Neurochemistry International, 81, 32–40.

    Article  CAS  PubMed  Google Scholar 

  50. Han, M. A., Woo, S. M., Min, K. J., Kim, S., Park, J. W., Kim, D. E., et al. (2015). 6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated cytochrome c release and down-regulation of c-FLIP(L) expression. Chemico-Biological Interactions, 228, 69–78.

    Article  CAS  PubMed  Google Scholar 

  51. Lee, H. E., Shin, J. A., Jeong, J. H., Jeon, J. G., Lee, M. H., & Cho, S. D. (2015). Anticancer activity of Ashwagandha against human head and neck cancer cell lines. Journal of Oral Pathology and Medicine,. doi:10.1111/jop.12353.

    Google Scholar 

  52. Park, M. H., Hong, J. E., Park, E. S., Yoon, H. S., Seo, D. W., Hyun, B. K., et al. (2015). Anticancer effect of tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression. Molecular Cancer, 14, 124.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Selim, S., & Al Jaouni, S. (2015). Anticancer and apoptotic effects on cell proliferation of diosgenin isolated from Costus speciosus (Koen.) Sm. BMC Complementary and Alternative Medicine, 15, 301.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Ammad Ahmad Farooqi

  2. Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari, Italy

    Cosmo Damiano Gadaleta, Girolamo Ranieri & Ilaria Marech

  3. Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan

    Sundas Fayyaz

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  1. Ammad Ahmad Farooqi
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  2. Cosmo Damiano Gadaleta
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Correspondence to Ammad Ahmad Farooqi.

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Farooqi, A.A., Gadaleta, C.D., Ranieri, G. et al. New Frontiers in Promoting TRAIL-Mediated Cell Death: Focus on Natural Sensitizers, miRNAs, and Nanotechnological Advancements. Cell Biochem Biophys 74, 3–10 (2016). https://doi.org/10.1007/s12013-015-0712-7

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