Skip to main content
SpringerLink
Log in

Programmed Cell Death, from a Cancer Perspective: An Overview

  • Review Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Programmed cell death (PCD) is probably the most widely discussed subject among the topics of cancer therapy. Over the last 2 decades an astonishing boost in our perception of cell death has been seen, and its role in cancer and cancer therapy has been thoroughly investigated. A number of discoveries have clarified the molecular mechanism of PCD, thus expounding the link between PCD and therapeutic tools. Even though PCD is assumed to play a major role in anticancer therapy, the clinical relevance of its induction remains uncertain. Since PCD involves multiple death programs including programmed necrosis and autophagic cell death, it has contributed to our better understanding of cancer pathogenesis and therapeutics. In this review, we discuss a brief outline of PCD types as well as their role in cancer therapeutics. Since irregularities in the cell death process are frequently found in various cancers, key proteins governing cell death type could be used as therapeutic targets for a wide range of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lockshin RA, Williams CM. Programmed cell death—II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J Insect Physiol. 1964;10:643–9.

    Article  CAS  Google Scholar 

  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  PubMed  CAS  Google Scholar 

  3. Jensen M, Engert A, Weissinger F, Knauf W, Kimby E, Poynton C, et al. Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell chronic lymphocytic leukemia. Invest New Drugs. 2008;26:139–49.

    Article  PubMed  CAS  Google Scholar 

  4. Baritaki S, Militello L, Malaponte G, Spandidos DA, Salcedo M, Bonavida B. The anti-CD20 mAb LFB-R603 interrupts the dysregulated NF-κB/Snail/RKIP/PTEN resistance loop in B-NHL cells: role in sensitization to TRAIL apoptosis. Int J Oncol. 2011;38:1683–94.

    PubMed  CAS  Google Scholar 

  5. Lockshin RA, Zakeri Z. Apoptosis, autophagy, and more. Int J Biochem Cell Biol. 2004;36:2405–19.

    Article  PubMed  CAS  Google Scholar 

  6. Tan ML, Ooi JP, Ismail N, Moad AIH, Muhammad TST. Programmed cell death pathways and current antitumor targets. Pharm Res. 2009;26:1547–60.

    Article  PubMed  CAS  Google Scholar 

  7. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta. 2010;1805:53–71.

    PubMed  CAS  Google Scholar 

  9. Mariño G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15:81–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, et al. Anti- and pro-tumor functions of autophagy. Nature. 1999;397:441–6.

    Article  PubMed  CAS  Google Scholar 

  12. Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2:277–88.

    Article  PubMed  CAS  Google Scholar 

  13. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487–501.

    Article  PubMed  CAS  Google Scholar 

  14. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281:1305–8.

    Article  PubMed  CAS  Google Scholar 

  15. Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem. 1997;272:32401–10.

    Article  PubMed  CAS  Google Scholar 

  16. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87:99–163.

    Article  PubMed  CAS  Google Scholar 

  17. Reed JC. Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol. 1997;34:9–19.

    PubMed  CAS  Google Scholar 

  18. Nasu Y, Benke A, Arakawa S, Yoshida GJ, Kawamura G, Manley S, Shimizu S, Ozawa T. In situ characterization of Bak clusters responsible for cell death using single molecule localization microscopy. Sci Rep. 2016;6:27505.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR. The BCL-2 family reunion. Mol Cell. 2010;37:299–310.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998;391:43–50.

    Article  PubMed  CAS  Google Scholar 

  21. Tewari M, Quan LT, O’Rourke K, Desnoyers S, Zeng Z, Beidler DR, et al. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995;81:801–9.

    Article  PubMed  CAS  Google Scholar 

  22. Schimmer AD. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. 2004;64:7183–90.

    Article  PubMed  CAS  Google Scholar 

  23. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55:178–94.

    Article  PubMed  Google Scholar 

  24. Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 1998;391:96–9.

    Article  PubMed  CAS  Google Scholar 

  25. Krysko DV, D’Herde K, Vandenabeele P. Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis. 2006;11:1709–26.

    Article  PubMed  Google Scholar 

  26. Ashkenazi A. Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev. 2008;19:325–31.

    Article  PubMed  CAS  Google Scholar 

  27. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30:87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Bai L, Wang S. Targeting apoptosis pathways for new cancer therapeutics. Annu Rev Med. 2014;65:139–55.

    Article  PubMed  CAS  Google Scholar 

  29. Stupack DG. Caspase-8 as a therapeutic target in cancer. Cancer Lett. 2013;332:133–40.

    Article  PubMed  CAS  Google Scholar 

  30. Wang S, Yu Q, Zhang R, Liu B. Core signaling pathways of survival/death in autophagy-related cancer networks. Int J Biochem Cell Biol. 2011;43:1263–6.

    Article  PubMed  CAS  Google Scholar 

  31. Pyo JO, Nah J, Jung YK. Molecules and their functions in autophagy. Exp Mol Med. 2012;44:73–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Liu B, Bao J-K, Yang J-M, Cheng Y. Targeting autophagic pathways for cancer drug discovery. Chin J Cancer. 2013;32:113–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Grasso D, Vaccaro MI. Macroautophagy and the oncogene-induced senescence. Front Endocrinol (Lausanne). 2014;5:157.

    PubMed  PubMed Central  Google Scholar 

  34. Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24:92–104.

    Article  PubMed  CAS  Google Scholar 

  35. Vakifahmetoglu-Norberg H, Kim M, Xia H-G, Iwanicki MP, Ofengeim D, Coloff JL, et al. Chaperone-mediated autophagy degrades mutant p53. Genes Dev. 2013;27:1718–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Han Q, Deng Y, Chen S, Chen R, Yang M, Zhang Z, et al. Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis. Sci Rep. 2017;7:4759.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Morselli E, Galluzzi L, Kepp O, Vicencio J-M, Criollo A, Maiuri MC, et al. Anti- and pro-tumor functions of autophagy. BBA-Mol Cell Res. 2009;1793:1524–32.

    CAS  Google Scholar 

  39. Shimizu S, Yoshida T, Tsujioka M, Arakawa S. Autophagic cell death and cancer. Int J Mol Sci. 2014;15:3145–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Gozuacik D, Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004;23:2891–906.

    Article  PubMed  CAS  Google Scholar 

  41. Arakawa S, Tsujioka M, Yoshida T, Sakurai HT, Nishida Y, Matsuoka Y, et al. Role of Atg5-dependent cell death in the embryonic development of Bax/Bak double-knockout mice. Cell Death Differ. 2017;24:1598–608.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Corcelle EA, Puustinen P, Jäättelä M. Apoptosis and autophagy: targeting autophagy signalling in cancer cells -’trick or treats’? FEBS J. 2009;276:6084–96.

    Article  PubMed  CAS  Google Scholar 

  43. Bhutia SK, Kegelman TP, Das SK, Azab B, Su Z-Z, Lee S-G, et al. Astrocyte elevated gene-1 induces protective autophagy. Proc Natl Acad Sci USA. 2010;107:22243–8.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yang J, Takahashi Y, Cheng E, Liu J, Terranova PF, Zhao B, et al. GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death. J Cell Sci. 2010;123:861–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Wu WKK, Cho CH, Lee CW, Wu YC, Yu L, Li ZJ, et al. Macroautophagy and ERK phosphorylation counteract the antiproliferative effect of proteasome inhibitor in gastric cancer cells. Autophagy. 2010;6:228–38.

    Article  PubMed  CAS  Google Scholar 

  46. Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol. 2000;150:1507–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan J-L, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181:497–510.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Suzuki K, Kubota Y, Sekito T, Ohsumi Y. Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells. 2007;12:209–18.

    Article  PubMed  CAS  Google Scholar 

  49. Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA. 2005;102:8204–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Inoki K, Li Y, Zhu T, Wu J, Guan K-L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4:648–57.

    Article  PubMed  CAS  Google Scholar 

  51. Shimizu S, Konishi A, Nishida Y, Mizuta T, Nishina H, Yamamoto A, Tsujimoto Y. Involvement of JNK in the regulation of autophagic cell death. Oncogene. 2010;29:2070–82.

    Article  PubMed  CAS  Google Scholar 

  52. Zhou Y-Y, Li Y, Jiang W-Q, Zhou L-F. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015;35(3):e00199.

    PubMed  PubMed Central  Google Scholar 

  53. Zhang Y, Chen P, Hong H, Wang L, Zhou Y, Lang Y. JNK pathway mediates curcumin-induced apoptosis and autophagy in osteosarcoma MG63 cells. Exp Ther Med. 2017;14:593–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 2009;9:537–49.

    Article  PubMed  CAS  Google Scholar 

  55. Masri J, Bernath A, Martin J, Jo OD, Vartanian R, Funk A, et al. mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor. Cancer Res. 2007;67:11712–20.

    Article  PubMed  CAS  Google Scholar 

  56. Wang MH, Sun R, Zhou XM, Zhang MY, Lu JB, Yang Y, et al. Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway. Cell Death Dis. 2018;9:2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W, et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736–48.

    Article  PubMed  CAS  Google Scholar 

  58. Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35:1–11.

    Article  PubMed  CAS  Google Scholar 

  59. Catena V, Fanciulli M. Deptor: not only a mTOR inhibitor. J Exp Clin Cancer Res. 2017;36:12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Hu B, Lv X, Gao F, Chen S, Wang S, Qing X, et al. Downregulation of DEPTOR inhibits the proliferation, migration, and survival of osteosarcoma through PI3K/Akt/mTOR pathway. Onco Targets Ther. 2017;10:4379.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS, Schutjens MH. Drug repositioning and repurposing: terminology and definitions in literature. Drug Discov Today. 2015;20(8):1027–34.

    Article  PubMed  Google Scholar 

  62. Tommasino C, Gambardella L, Buoncervello M, Griffin RJ, Golding BT, Alberton M, et al. New derivatives of the antimalarial drug Pyrimethamine in the control of melanoma tumor growth: an in vitro and in vivo study. J Exp Clin. Cancer Res. 2016;35(1):137.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Yoshida GJ. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. J Hematol Oncol. 2017;10:67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Chang C, Simmons DT, Martin MA, Mora PT. Identification and partial characterization of new antigens from simian virus 40-transformed mouse cells. J Virol. 1979;31:463–71.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci USA. 1979;76:2420–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Kress M, May E, Cassingena R, May P. Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. J Virol. 1979;31:472–83.

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979;278:261–3.

    Article  PubMed  CAS  Google Scholar 

  68. Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J, et al. Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz.). 2013;61:43–58.

    Article  CAS  Google Scholar 

  69. Rotter V. p53, a transformation-related cellular-encoded protein, can be used as a biochemical marker for the detection of primary mouse tumor cells. Proc Natl Acad Sci USA. 1983;80:2613–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Balaburski GM, Hontz RD, Murphy ME. p53 and ARF: unexpected players in autophagy. Trends Cell Biol. 2010;20:363–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Budanov AV, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 2008;134:451–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Crighton D, Wilkinson S, O’Prey J, Syed N, Smith P, Harrison PR, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126:121–34.

    Article  PubMed  CAS  Google Scholar 

  73. Crighton D, O’Prey J, Bell HS, Ryan KM. p73 regulates DRAM-independent autophagy that does not contribute to programmed cell death. Cell Death Differ. 2007;14:1071–9.

    Article  PubMed  CAS  Google Scholar 

  74. Newton K, Manning G. Necroptosis and Inflammation. Annu Rev Biochem. 2016;85:743–63.

    Article  PubMed  CAS  Google Scholar 

  75. Su Z, Yang Z, Xu Y, Chen Y, Yu Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 2015;14:48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Cho YS, Park SY. Harnessing of programmed necrosis for fighting against cancers. Biomol Ther (Seoul). 2014;22:167–75.

    Article  CAS  Google Scholar 

  77. Wang T, Jin Y, Yang W, Zhang L, Jin X, Liu X, et al. Necroptosis in cancer: an angel or a demon? Tumour Biol. 2017;39:1–11.

    Google Scholar 

  78. Chan FK-M. Programmed necrosis/necroptosis: an inflammatory form of cell death. In: Wu H, editor. Cell death: mechanism and disease. New York: Springer; 2014. p. 211–28.

    Chapter  Google Scholar 

  79. Ch’en IL, Tsau JS, Molkentin JD, Komatsu M, Hedrick SM. Mechanisms of necroptosis in T cells. J Exp Med. 2011;208:633–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Lu JV, Chen HC, Walsh CM. Necroptotic signaling in adaptive and innate immunity. Semin Cell Dev Biol. 2014;35:33–9.

    Article  PubMed  CAS  Google Scholar 

  81. Dempsey LA. Interferon-induced necroptosis. Nat Immunol. 2013;14:892.

    Google Scholar 

  82. He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci USA. 2011;108:20054–9.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1:112–9.

    Article  PubMed  CAS  Google Scholar 

  84. Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T. The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal. 2010;3:4.

    Article  CAS  Google Scholar 

  85. Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 2010;11:700–14.

    Article  PubMed  CAS  Google Scholar 

  86. Wright A, Reiley WW, Chang M, Jin W, Lee AJ, Zhang M, et al. Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev Cell. 2007;13:705–16.

    Article  PubMed  CAS  Google Scholar 

  87. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114:181–90.

    Article  PubMed  CAS  Google Scholar 

  88. Lin Y, Devin A, Rodriguez Y, Liu ZG. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 1999;13:2514–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Christofferson DE, Yuan J. Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol. 2010;22:263–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148:213–27.

    Article  PubMed  CAS  Google Scholar 

  91. Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 2011;43:432–48.

    Article  PubMed  CAS  Google Scholar 

  92. Xu YZ, Kanagaratham C, Youssef M, Radzioch D. New frontiers in cancer chemotherapy—targeting cell death pathways. In: Najman S, editor. Cell biology—new insights. Rijeka: InTech; 2016. p. 93–140.

    Google Scholar 

  93. Su Z, Yang Z, Xu Y, Chen Y, Yu Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 2015;14:48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Fu Z, Deng B, Liao Y, Shan L, Yin F, Wang Z, et al. The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis. BMC Cancer. 2013;13:580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Buchheit CL, Rayavarapu RR, Schafer ZT. The regulation of cancer cell death and metabolism by extracellular matrix attachment. Semin Cell Dev Biol. 2012;23:402–11.

    Article  PubMed  CAS  Google Scholar 

  96. Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 2016;26:165–76.

    Article  PubMed  CAS  Google Scholar 

  98. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156:317–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R, Gu W, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520:57–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X. Ferroptosis is an autophagic cell death process. Cell Res. 2016;26(9):1021–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Cho YS, Park HL. Exploitation of necroptosis for treatment of caspase-compromised cancers. Oncol Lett. 2017;14:1207–14.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Los M, Mozoluk M, Ferrari D, Stepczynska A, Stroh C, Renz A, et al. Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell. 2002;13:978–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Vandenabeele P, Vanden Berghe T, Festjens N. Caspase inhibitors promote alternative cell death pathways. Sci STKE. 2006;6:pe44.

    Google Scholar 

  104. Lu JV, Weist BM, van Raam BJ, Marro BS, Nguyen LV, Srinivas P, et al. Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc Natl Acad Sci USA. 2011;108:15312–7.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Nigam M, Ranjan V, Srivastava S, Sharma R, Balapure AK. Centchroman induces G0/G1 arrest and caspase-dependent apoptosis involving mitochondrial membrane depolarization in MCF-7 and MDA MB-231 human breast cancer cells. Life Sci. 2008;82:577–90.

    Article  PubMed  CAS  Google Scholar 

  106. Nigam M, Singh N, Ranjan V, Zaidi D, Sharma R, Nigam D, et al. Centchroman mediated apoptosis involves cross-talk between extrinsic/intrinsic pathways and oxidative regulation. Life Sci. 2010;87:750–8.

    Article  PubMed  CAS  Google Scholar 

  107. Singh N, Nigam M, Ranjan V, Sharma R, Balapure AK, Rath SK. Caspase mediated enhanced apoptotic action of cyclophosphamide- and resveratrol-treated MCF-7 cells. J Pharmacol Sci. 2009;109:473–85.

    Article  PubMed  CAS  Google Scholar 

  108. Sharifi-Rad J, Sureda A, Tenore GC, Daglia M, Sharifi-Rad M, Valussi M, Tundis R, Sharifi-Rad M, Loizzo MR, Ademiluyi AO, Sharifi-Rad R, Ayatollahi SA, Iriti M. Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules. 2017;22:70.

    Article  CAS  PubMed Central  Google Scholar 

  109. Singh N, Nigam M, Ranjan V, Zaidi D, Garg VK, Sharma S, et al. Resveratrol as an adjunct therapy in cyclophosphamide-treated MCF-7 cells and breast tumor explants. Cancer Sci. 2011;102:1059–67.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal, Uttarakhand, 246174, India

    Abhay P. Mishra

  2. Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Bahare Salehi

  3. Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol, 61663335, Iran

    Mehdi Sharifi-Rad

  4. OU Endocrinology, Dept. Medicine (DIMED), University of Padova, via Ospedale 105, 35128, Padua, Italy

    Raffaele Pezzani

  5. AIROB, Associazione Italiana per la Ricerca Oncologica di Base, Padua, Italy

    Raffaele Pezzani

  6. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farzad Kobarfard & Javad Sharifi-Rad

  7. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farzad Kobarfard

  8. Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB, Canada

    Javad Sharifi-Rad

  9. Department of Biochemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal, Uttarakhand, 246174, India

    Manisha Nigam

Authors
  1. Abhay P. Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bahare Salehi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehdi Sharifi-Rad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raffaele Pezzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farzad Kobarfard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Javad Sharifi-Rad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manisha Nigam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Javad Sharifi-Rad or Manisha Nigam.

Ethics declarations

Conflict of interest

Abhay P. Mishra, Bahare Salehi, Mehdi Sharifi-Rad, Raffaele Pezzani, Farzad Kobarfard, Javad Sharifi-Rad and Manisha Nigam declare no conflict of interest.

Funding

The authors have no funding to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mishra, A.P., Salehi, B., Sharifi-Rad, M. et al. Programmed Cell Death, from a Cancer Perspective: An Overview. Mol Diagn Ther 22, 281–295 (2018). https://doi.org/10.1007/s40291-018-0329-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-018-0329-9

Search

Navigation