Review Article

Cellular Senescence and Anti-Cancer Therapy

Author(s): Jieqiong You, Rong Dong, Meidan Ying, Qiaojun He, Ji Cao * and Bo Yang*

Volume 20 , Issue 7 , 2019

Page: [705 - 715] Pages: 11

DOI: 10.2174/1389450120666181217100833

Price: $65


Background: Cellular senescence is generally understood as a permanent cell cycle arrest stemming from different causes. The mechanism of cellular senescence-induced cell cycle arrest is complex, involving interactions between telomere shortening, inflammations and cellular stresses. In recent years, a growing number of studies have revealed that cellular senescence could mediate the cancer progression of neighboring cells, but this idea is controversial and contradictory evidence argues that cellular senescence also contributes to tumor suppression.

Objective: Given that the complicated role of senescence in various physiological and pathological scenarios, we try to clarify the precise contribution role of cellular senescence to tumor progression.

Methods: Search for the information in a large array of relevant articles to support our opinion.

Results: We discuss the relatively widespread occurrence of cellular senescence in cancer treatment and identify the positive and negative side of senescence contributed to tumor progression.

Conclusion: We argue that the availability of pro-senescence therapy could represent as a promising regimen for managing cancer disease, particularly with regard to the poor clinical outcome obtained with other anticancer therapies.

Keywords: Cellular senescence, biomarkers, mechanism, cancer therapy, drug in combination, tumor suppression.

Next »
Graphical Abstract
Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37: 614-36.
He S, Sharpless NE. Senescence in Health and Disease. Cell 2017; 169(6): 1000-11.
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010; 24(22): 2463-79.
Ruhland M, Coussens LM, Stewart S. Senescence and cancer: An evolving inflammatory paradox. Biochim Biophys Acta 2016; 1865(1): 14-22.
Muñozespín D, Cañamero M, Maraver A, et al. Programmed cell senescence during mammalian embryonic development. Cell 2013; 155(5): 1104-18.
Storer M, Mas A, Robertmoreno A, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 2013; 155(5): 1119-30.
Allsopp RC, Vaziri H, Patterson C, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992; 89(21): 10114-8.
Smogorzewska A, De LT. Regulation of telomerase by telomeric proteins. Annu Rev Biochem 2004; 73(1): 177-208.
Takai H, Smogorzewska A, De LT. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13(17): 1549-56.
Collins K, Mitchell JR. Telomerase in the human organism. Oncogene 2002; 21(4): 564-79.
Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet 2010; 11(5): 319-30.
Stewart SA, Weinberg RA. Telomeres: Cancer to Human Aging. Annu Rev Cell Dev Biol 2006; 22(22): 531-57.
Feldser DM, Greider CW. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell 2007; 11(5): 461-9.
Burton DGA, Faragher RGA. Cellular senescence: from growth arrest to immunogenic conversion. Age 2015; 37(2): 27.
Serrano M, Lin AW, Mccurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4A. Cell 1997; 88(5): 593-602.
Michaloglou C, Vredeveld LCW, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nat 2005; 436(7051): 720-4.
Petti C, Molla A, Vegetti C, et al. Coexpression of NRASQ61R and BRAFV600E in human melanoma cells activates senescence and increases susceptibility to cell-mediated cytotoxicity. Cancer Res 2006; 66(13): 6503-11.
Sun P, Yoshizuka N, New L, et al. PRAK is essential for ras-induced senescence and tumor suppression. Cell 2007; 128(2): 295-308.
Courtoiscox S, Williams SMG, et al. A negative feedback signaling network underlies oncogene-induced senescence. Cancer Cell 2006; 10(6): 459-72.
Micco RD, Fumagalli M, Fagagna FDAD. Breaking news: high-speed race ends in arrest–how oncogenes induce senescence. Trends Cell Biol 2007; 17(11): 529-36.
Wang G, Fu Y, Hu F, et al. Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway. Cell Death Dis 2017; 8(2): e2607.
Chen Z, Trotman LC, Shaffer D, et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nat 2005; 436(7051): 725-30.
Bainor AJ, Deng FM, Wang Y, et al. Chromatin-associated protein SIN3B prevents prostate cancer progression by inducing senescence. Cancer Res 2017; 77(19): 5339.
Young AP, Schlisio S, Minamishima YA, et al. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 2008; 10(3): 361-9.
Ma C, Wang F, Han B, et al. SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex. Mol Cancer 2018; 17(1): 78.
Ma Y, Jiang J, Zhang Y, et al. IGFBP-rP1 acts as a potential tumor suppressor via the suppression of ERK signaling pathway in endometrial cancer cells. Mol Med Rep 2017; 16(2): 1445-50.
Kim KS, Kim JE, Choi KJ, Bae S, Kim DH. Characterization of DNA damage-induced cellular senescence by ionizing radiation in endothelial cells. Int J Radiat Biol 2014; 90(1): 71.
Ou HL, Schumacher B. DNA damage responses and p53 in the aging process. Blood 2018; 131(5): 488.
Mo J, Sun B, Zhao X, et al. Hypoxia-induced senescence contributes to the regulation of microenvironment in melanomas. Pathol Res Pract 2013; 209(10): 640-7.
Lu T, Finkel T. Free radicals and senescence. Exp Cell Res 2008; 314(9): 1918-22.
Mehta IS, Figgitt M, Clements CS, Kill IR, Bridger JM. Alterations to nuclear architecture and genome behavior in senescent cells. Ann N Y Acad Sci 2007; 1100(1): 250-63.
Narita M, Nũnez S, Heard E, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 2003; 113(6): 703-16.
Zhang R, Chen W, Adams PD. Molecular dissection of formation of senescence-associated heterochromatin foci. Mol Cell Biol 2007; 27(6): 2343-58.
Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995; 92(20): 9363-7.
Reznikoff CA, Yeager TR, Belair CD, et al. Elevated p16 at senescence and loss of p16 at immortalization in human papillomavirus 16 E6, but not E7, transformed human uroepithelial cells. Cancer Res 1996; 56(13): 2886-90.
D'Adda dFF, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nat 2003; 426(6963): 194.
Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13(17): 1549-56.
Zhang R, Poustovoitov MV, Ye X, et al. Formation of macroh2a-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 2005; 8(1): 19-30.
Costanzi C, Pehrson JR. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nat 1998; 393(6685): 599-601.
Narita M, Narita M, Krizhanovsky V, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 2006; 126(3): 503.
Rugang Zhang WC, Peter D. Adams. Molecular dissection of formation of senescence-associated heterochromatin foci. Mol Cell Biol 2007; 27(6): 2343-58.
Trojer P, Reinberg D. Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell 2007; 28(1): 1-13.
Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005; 120(4): 513-22.
Kuilman T, Peeper DS. Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 2009; 9(2): 81-94.
Vandenberk B, Brouwers B, Hatse S, Wildiers H. p16INK4a: A central player in cellular senescence and a promising aging biomarker in elderly cancer patients. J Geriatr Oncol 2011; 2(4): 259-69.
Bai P, Xiao X, Zou J, et al. Expression of p14(ARF), p15(INK4b), p16(INK4a) and skp2 increases during esophageal squamous cell cancer progression. Exp Ther Med 2012; 3(6): 1026-32.
Chen W, Kang J, Xia J, et al. p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts. Int J Mol Med 2008; 21(5): 645.
Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004; 432(7015): 307-15.
Cánepa ET, Scassa ME, Ceruti JM, et al. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life 2007; 59(7): 419.
Rusin M, Zajkowicz AD. Resveratrol induces senescence-like growth inhibition of U-2 OS cells associated with the instability of telomeric DNA and upregulation of BRCA1. Mech Ageing Dev 2009; 130(8): 528-37.
Jackson JG, Pereira-Smith OM. p53 is preferentially recruited to the promoters of growth arrest genes p21 and GADD45 during replicative senescence of normal human fibroblasts. Cancer Res 2006; 66(17): 8356.
Harbour JW, Luo RX, Santi AD, Postigo AA, Dean DC. Cdk Phosphorylation Triggers Sequential Intramolecular Interactions that Progressively Block Rb Functions as Cells Move through G1. Cell 1999; 98(6): 859.
Quelle DE, Zindy F, Ashmun RA, Sherr CJ. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 1995; 83(6): 993-1000.
Collins CJ, Sedivy JM. Involvement of the INK4a/Arf gene locus in senescence. Aging Cell 2003; 2(3): 145-50.
Matheu A, Maraver A, Serrano M. The Arf/p53 pathway in cancer and aging. Cancer Res 2008; 68(15): 6031.
Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006; 6(12): 909-23.
Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell 2007; 130(2): 223-33.
Artandi SE, Depinho RA. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 2000; 10(1): 39-46.
Artandi SE, Chang S, Lee SL, et al. Telomere dysfunction promotes non-reciprocal translocations and epithelialcancers in mice. Nat 2000; 406(6796): 641.
Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer 2008; 8(6): 450-8.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-76.
Banito A, Rashid ST, Acosta JC, et al. Senescence impairs successful reprogramming to pluripotent stem cells. Gend Dev 2009; 23(18): 2134.
Koch CM, Reck K, Shao K, et al. Pluripotent stem cells escape from senescence-associated DNA methylation changes. Genome Res 2013; 23(2): 248.
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2015; 16(1): 1-5.
Frobel J, Hemeda H, Lenz M, et al. Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells. Stem Cell Reports 2014; 3(3): 414-22.
Bork S, Pfister S, Witt H, et al. DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 2010; 9(1): 54-63.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646.
Grayschopfer VC, Cheong SC, Chong H, et al. Cellular senescence in naevi and immortalisation in melanoma: a role for p16? BJC 2006; 95(4): 496.
Michaloglou C, Vredeveld LC, Mooi WJ, Peeper DS. BRAF(E600) in benign and malignant human tumours. Oncogene 2008; 27(7): 877.
Mooi WJ, Peeper DS. Oncogene-induced cell senescence--halting on the road to cancer. N Engl J Med 2006; 355(10): 1037-46.
Lehners N, Ellert E, Xu J, et al. Oncogene-induced senescence: a potential breakpoint mechanism against malignant transformation in plasma cell disorders. Leuk Lymphoma 2018; 1-10.
Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nat 2006; 444(7119): 633-7.
Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 2010; 5(1): 99-118.
Demaria M, O’Leary MN, Chang J, et al. Cellular Senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov 2017; 7(2): 165.
Ritschka B, Storer M, Mas A, et al. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Gend Dev 2017; 31(2): 172.
Ortizmontero P, Londoñovallejo A, Vernot JP. Senescence-associated IL-6 and IL-8 cytokines induce a self- and cross-reinforced senescence/inflammatory milieu strengthening tumorigenic capabilities in the MCF-7 breast cancer cell line. Cell Commun Signal 2017; 15(1): 17.
Soto-Gamez A, Demaria M. Therapeutic interventions for aging: the case of cellular senescence. Drug Discov Today 2017; 22(5): 786.
Laberge RM, Sun Y, Orjalo AV, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 2015; 17(8): 1049.
Schmitt CA, Fridman JS, Yang M, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002; 109(3): 335-46.
Hornsby PJ. Senescence as an anticancer mechanism. J Clin Oncol 2007; 25(14): 1852.
Chang BD, Watanabe K, Broude EV, et al. Effects of p21waf1/cip1/sdi1on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases. Proc Natl Acad Sci 2000; 97(8): 4291.
Hannon GJ, Beach D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nat 1994; 371(6494): 257-61.
Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Sci 1994; 264(5157): 436-40.
Sharpless NE. Ink4a/Arf links senescence and aging. Exp Gerontol 2004; 39(11): 1751-9.
Matsuoka S, Edwards MC, Bai C, et al. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Gend Dev 1995; 9(9): 650-62.
Xue W, Zender L, Miething C, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nat 2007; 445(7128): 656.
Donninger H, Barnoud T, Clark GJ. NORE1A is a double barreled Ras senescence effector that activates p53 and Rb. Cell Cycle 2016; 15(17): 2263-4.
Donninger H, Calvisi DF, Barnoud T, et al. NORE1A is a Ras senescence effector that controls the apoptotic/senescent balance of p53 via HIPK2. J Cell Biol 2015; 208(6): 777-89.
Barnoud T, Schmidt ML, Donninger H, Clark GJ. The role of the NORE1A tumor suppressor in Oncogene-Induced Senescence. Cancer Lett 2017; 400: 30-6.
Roninson IB. Tumor cell senescence in cancer treatment. Cancer Res 2003; 63(11): 2705.
Weinstein IB, Joe A. Oncogene addiction. Cancer Res 2008; 68(9): 3077.
Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 2009; 138(4): 807.
Nomura T, Kinuta M, Hongyo T, Nakajima H, Hatanaka T. Programmed Cell death in whole body and organ systems by low dose radiation. J Radiation Res1992 33 Suppl(1): 109.
Hermanns C, Hampl V, Holzer K, et al. The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma. Oncogene 2017; 36(24): 3464-76.
Zhang H, Cohen SN. Smurf2 up-regulation activates telomere-dependent senescence. Gend Dev 2004; 18(24): 3028-40.
Zhang H, Teng Y, Kong Y, Kowalski PE, Cohen SN. Suppression of human tumor cell proliferation by Smurf2-induced senescence. J Cell Physiol 2008; 215(3): 613-20.
Zhu H, Ren S, Bitler BG, et al. SPOP E3 ubiquitin ligase adaptor promotes cellular senescence by degrading the SENP7 deSUMOylase. Cell Reports 2015; 13(6): 1183-93.
Hall AHS, Alexander KA. RNA interference of human papillomavirus type 18 e6 and e7 induces senescence in hela cells. J Virol 2003; 77(10): 6066-9.
Sima N, Kong DB, Wang W, et al. Antisense targeting to human papillomavirus 18 E6/E7 affects the proliferation and apoptosis of human cervical carcinoma: an in vitro experiment with HeLa cells. Natl Med J China 2007; 87(23): 1618.
Shammas MA, Koley H, Batchu RB, et al. Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett’s adenocarcinoma cells: mechanism and therapeutic potential. Mol Cancer 2005; 4(1): 24.
Park C, Lee I, Kang WK. E2F-1 is a critical modulator of cellular senescence in human cancer. Int J Mol Med 2006; 17(5): 715.
Park C, Lee I, Kang WK. Influence of small interfering RNA corresponding to ets homologous factor on senescence-associated modulation of prostate carcinogenesis. Mol Cancer Ther 2006; 5(12): 3191.
Xu D, Takeshita F, Hino Y, et al. miR-22 represses cancer progression by inducing cellular senescence. J Cell Biol 2011; 193(2): 409-24.
Ye Z, Fang J, Dai S, et al. Microrna-34a induces a senescence-like change via the down-regulation of SIRT1 and up-regulation of p53 protein in human esophageal squamous cancer cells with a wild-type p53 gene background. Cancer Lett 2015; 370(2): 216.
Xu X, Kim JJ, Li Y, et al. Oxidative stress-induced miRNAs modulate AKT signaling and promote cellular senescence in uterine leiomyoma. J Mol Med 2018; 1-12.
Wang N, Zhu C, Xu Y, Qian W, Zheng M. Negative regulation of pten by microrna-221 and its association with drug resistance and cellular senescence in lung Cancer Cells. BioMed Res Int 2018; 2018; 2018: 7908950.
Chai C, Song LJ, Han SY, Li XQ, Li M. MicroRNA‐21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway. CNS Neurosci Ther 2018; 24(5): 369-80.
Panganiban RAM, Snow AL, Day RM. Mechanisms of Radiation toxicity in transformed and non-transformed cells. Int J Mol Sci 2013; 14(8): 15931-58.
Hendry JH, Potten CS. Intestinal cell radiosensitivity: a comparison for cell death assayed by apoptosis or by a loss of clonogenicity. Int J Radiat Biol 1982; 42(6): 621-8.
Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: Relevance to radiotherapy. Int J Radiat Oncol Biol Phys 1995; 33(4): 781-96.
Hendry JH, Potten CS, Merritt A. Apoptosis induced by high- and low-LET radiations. Radiat Environ Biophys 1995; 34(1): 59-62.
Ross GM. Induction of cell death by radiotherapy. Endocrinerelated cancer 1999; 6(1): 41.
Oh CW, Bump EA, Kim JS, Janigro D, Mayberg MR. Induction of a senescence-like phenotype in bovine aortic endothelial cells by ionizing radiation. Radiat Res 2001; 156(3): 232-40.
Igarashi K, Sakimoto I, Kataoka K, Ohta K, Miura M. Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells. Exp Cell Res 2007; 313(15): 3326-36.
Suzuki K, Mori I, Nakayama Y, et al. Radiation-induced senescence-like growth arrest requires tp53 function but not telomere shortening. Radiat Res 2001; 155(1): 248-53.
Jones KR, Elmore LW, Jacksoncook C, et al. p53-Dependent accelerated senescence induced by ionizing radiation in breast tumour cells. Int J Radiat Biol 2005; 81(6): 445-58.
Luo H, Yount C, Lang H, et al. Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence. Lung Cancer 2013; 81(2): 167-73.
Penha RCC, Lima SCS, Pinto LFR, Fusco A. Radiation-induced senescence and thyroid cancer: a barrier or a driving force. PAJAR 2015; 3(1): 29.
Podtcheko A, Namba H, Saenko V, et al. Radiation-induced senescence-like terminal growth arrest in thyroid cells. Thyroid 2005; 15(4): 306-13.
Day RM, Snow AL, Panganiban RA. Radiation-induced accelerated senescence: A fate worse than death? Cell Cycle 2014; 8(13): 2011-2.
Sang BK, Bozeman R, Kaisani A, et al. Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses. Oncogene 2016; 35(26): 3365-75.
Yang PM. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells. Autophagy 2014; 10(7): 1212-28.
Chen WS, Yu YC, Lee YJ, et al. Depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells regardless of functional p53 expression. Int J Radiat Oncol Biol Phys 2010; 77(2): 566-74.
Skinner HD, Sandulache VC, Ow TJ, et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res 2012; 18(1): 290.
Yu YC, Yang PM, Chuah QY, et al. Radiation-induced senescence in securin-deficient cancer cells promotes cell invasion involving the IL-6/STAT3 and PDGF-BB/PDGFR pathways. Scientific Reports 2013; 3(4): 1675.
Kahlem P, Dörken B, Schmitt CA. Cellular senescence in cancer treatment: friend or foe? J Clin Invest 2004; 113(2): 169-74.
Joyner DE, Albritton KH, Bastar JD, Randall RL. G3139 antisense oligonucleotide directed against antiapoptotic Bcl-2 enhances doxorubicin cytotoxicity in the FU-SY-1 synovial sarcoma cell line. J Orthop Res 2006; 24(3): 474-80.
Jackson JG, Pereirasmith O. Primary and compensatory roles of the RB family members in cell cycle gene regulation during the induction of the senescent like phenotype in doxorubicin treated MCF-7 cells. Cancer Res 2006; 66.
Ota H, Tokunaga E, Chang K, et al. Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 2005; 25(2): 176-85.
Perrigue PM, Najbauer J, Barciszewski J. Histone demethylase JMJD3 at the intersection of cellular senescence and cancer. Biochim Biophys Acta 2016; 1865(2): 237-44.
Efeyan A, Ortega-Molina A, Velasco-Miguel S, et al. Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin. Cancer Res 2007; 67(15): 7350-7.
Xu B, Deng Y, Bi R, et al. A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification. Cancer Chemother Pharmacol 2018; 81(6): 1083.
Oladghaffari M, Islamian JP, Baradaran B, Monfared AS. MLN4924 therapy as a novel approach in cancer treatment modalities. J Chemother 2016; 28(2): 74-82.
Kim HD, Jang CY, Choe JM, Sohn J, Kim J. Phenylbutyric acid induces the cellular senescence through an Akt/p21 WAF1 signaling pathway. Biochem Biophys Res Commun 2012; 422(2): 213-8.
Bruyère C, Mathieu V, Vessières A, et al. Ferrocifen derivatives that induce senescence in cancer cells: selected examples. J Inorg Biochem 2014; 141: 144-51.
Mumcuoglu M, Gurkanalp AS, Buyukbingol E, Cetinatalay R. Retinoid N-(1H-benzo[d]imidazol-2-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide induces p21-dependent senescence in breast cancer cells. Steroids 2016; 108: 31-8.
Naresh A, Venkateswara RM, Kotapalli SS, Ummanni R, Venkateswara RB. Oxazolidinone derivatives: cytoxazone-linezolid hybrids induces apoptosis and senescence in DU145 prostate cancer cells. Eur J Med Chem 2014; 80: 295-307.
Chu PY, Liu MY. Amino acid cysteine induces senescence and decelerates cell growth in melanoma. J Funct Foods 2015; 18: 455-62.
Rosenberg SA. Decade in review-cancer immunotherapy: entering the mainstream of cancer treatment. Nat Rev Clin Oncol 2014; 11(11): 630-2.
Speer TW. CD20 Surface Antigen. In: Encyclopedia of Radiation Oncol. 2013; p. 97.
Dabritz JH, Yu Y, Milanovic M, et al. CD20-targeting immunotherapy promotes cellular senescence in B-cell lymphoma. Mol Cancer Ther 2016; 15(5): 1074-81.
Braumüller H, Wieder T, Brenner E, et al. T-helper-1-cell cytokines drive cancer into senescence. Nat 2013; 494(7437): 361-5.
Hubackova S, Kucerova A, Michlits G, et al. IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2. Oncogene 2016; 35(10): 1236-49.
Deursen JMV. The role of senescent cells in ageing. Nat 2014; 509(7501): 439-46.
Rao SG, Jackson JG. SASP: Tumor suppressor or promoter? Yes! Trends Cancer 2016; 2(11): 676-87.
Dga B, Stolzing A. Cellular senescence: immunosurveillance and future immunotherapy. Ageing Res Rev 2018; 43: 17-25.
Kasakovski D, Xu L, Li Y. T cell senescence and CAR-T cell exhaustion in hematological malignancies. J Hematol Oncol 2018; 11(1): 91.
Orimo A, Weinberg RA. Stromal fibroblasts in cancer: A Novel tumor-promoting cell type. Cell Cycle 2006; 5(15): 1597-601.
Ruhland MK, Loza AJ, Capietto AH, et al. Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun 2016; 7: 11762.
Tato-Costa J, Casimiro S, Pacheco T, et al. Therapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancer. Clin Colorectal Cancer 2015; 15(2): 170-8. e3.
Watanabe S, Kawamoto S, Ohtani N, Hara E. Impact of senescence‐associated secretory phenotype and its potential as a therapeutic target for senescence‐associated diseases. Cancer Sci 2017; 108(4): 563-9.
Hou J, Cui C, Kim S, Sung C, Choi C. Ginsenoside F1 suppresses astrocytic senescence-associated secretory phenotype. Chem Biol Interact 2018; 283: 75-80.
Alimbetov D, Davis T, Brook AJC, et al. Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2. Biogerontol 2016; 17(2): 305-15.
Zhao Y, Tu MJ, Yu YF, et al. Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth. Biochem Pharmacol 2015; 98(4): 602-13.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy