Meme Kanser Hücrelerinde Kanser Kaynaklı İlaç Direnci Ve Bağışıklıktan Kaçınmanın Kavşağında Ferroptoz

Yıl 2024, Cilt: 2 Sayı: 2, 30 - 38, 31.08.2024

Çiğdem Çiçekli , Zekiye Altun , Mustafa Nusret Çiçekli

Öz

Demire olan bağımlılıkları, kanser hücrelerini ferroptoz olarak bilinen demir katalizli nekroza daha duyarlı hale getirir. Günümüze kadar elde edilen veriler, ferroptotik hücre ölümünün tümör büyümesinin baskılanmasına yol açtığını göstermektedir. Ferroptozu hedeflemek umut verici bir antikanser stratejisi olabilir. Bu sebeple ferroptozu indükleyen ajanların keşfinin devamlılığı ve ferroptozda yer alan düzenleyici mekanizmaların ve ilgili genlerin daha fazla tanımlanması, kanser tedavisinde ferroptozu hedeflemek için stratejiler geliştirmeye bir temel oluşturabilir. Ferroptoz duyarlılığını düzenleyen bu süreçlerin daha iyi anlaşılması, nihayetinde kanser tedavisini geliştirmek için yeni terapötik stratejilerin keşfedilmesine yardımcı olmalıdır. Yapılan çalışmalar doğrultusunda üçlü negatif meme kanserinin ferroptoza karşı ER pozitif meme kanserinden daha duyarlı olduğu belirtilmiştir. Meme kanseri tedavisindeki en önemli sorun, metastaz ve ilaç direncine bağlı ortaya çıkan ölümdür. Tedavide en sık kullanılan kemoterapötik ajanlardan biri ise Doksorubisin (Dox) olup, tedaviye bağlı direnç nedeniyle hastaların önemli bir kısmı kaybedilmektedir. Dox direncinin yenilmesinde farklı hücre ölüm tiplerini tetikleyecek ajanların hedeflenmesi önemli bir konudur ve son zamanlarda ferroptotik yolak üzerinden kanser hücrelerinin hedeflenmesi ilgi odağı haline gelmektedir. Sonuç olarak, tedaviye dirençli kanserlerde kanser hücrelerini ölüme sürükleme potansiyeli açısından ferroptotik hücre ölüm mekanizmasının tetiklenmesi direnci yenme açısından umut verici yeni bir yaklaşım olarak değerlendirilmektedir. Bu derlemede ferroptotik hücre ölümü ve meme kanseri tedavi direnci açısından olası moleküler etki mekanizmaları gözden geçirilmiştir.

Anahtar Kelimeler

Ferroptoz, Meme Kanseri, İlaç Direnci, Kanser

Etik Beyan

Yoktur

Destekleyen Kurum

Yoktur

Teşekkür

Yoktur

The Relationship Between Drug Resistance And Ferroptosis in Breast Cancer Cells Ferroptotic Process in Breast Cancer

Öz

Because of their iron-dependent nature, cancer cells are more prone to ferroptosis, an iron-catalyzed necrosis. Accumulating evidence suggests that ferroptotic cell death leads to suppression of tumor growth. Targeting ferroptosis could be a promising anticancer strategy. Recent discoveries of ferroptosis-inducing agents and further identification of the regulatory mechanisms and genes involved in ferroptosis provide a basis for developing strategies to target ferroptosis in cancer therapy. Therefore, a better understanding of the processes that regulate ferroptosis sensitivity should ultimately aid the discovery of new therapeutic strategies to improve cancer therapy. In line with the studies, they found that triple-negative breast cancer is more sensitive to ferroptosis than ER-positive breast cancer. The most essential problem in breast cancer treatment is death due to metastasis and drug resistance. Doxorubicin (Dox) is one of the most commonly used chemotherapeutic agents in treatment, and a significant portion of patients die due to treatment-related resistance. Targeting agents that will trigger different types of cell death in overcoming Dox resistance is an important issue, and targeting cancer cells via the ferroptotic pathway has recently become the focus of attention. In conclusion, triggering the ferroptotic cell death mechanism is considered a promising new approach in overcoming resistance in terms of the potential to drive cancer cells to death in treatment-resistant cancers. In this review, possible molecular mechanisms of action in terms of ferrroptotic cell death and breast cancer treatment resistance and reviewed.

Anahtar Kelimeler

Ferroptosis, Breast cancer, Drug resistance, Cancer

Etik Beyan

None

Destekleyen Kurum

None

Teşekkür

None

Kaynakça

• Koçtürk AS, Vatansever HS, Altun ZS. Hastalıkta ve sağlıkta hücre ölümü mekanizmaları ve deneysel araştırma modelleri. Hücre ölümü araştırma derneği, 2022, Celal Bayar Üniversitesi basımevi.
• Tozkoparan B, Peri Aytaç S. Kanser kemoterapisinde terapötik hedef olarak glutatyon S-transferazlar. Hacettepe Üniversitesi, Eczacılık Fakültesi Dergisi 2007;7(2):139-64.
• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin. 2021 Jan;71(1): 7-33.
• Telli ML, Gradishar WJ, Ward JH. NCCN Guidelines updates: breast cancer. J Natl Compr Canc Netw. 2019 May 1;17(5.5): 552-555. Stefanis L. Alpha-synuclein in Parkinson's disease. Cold Spring Harb Perspect Med. 2012 Feb; 2(2): a009399.
• Ma S, Dielschneider RF, Henson ES, Xiao W, Choquette TR, Blankstein AR, et al. Ferroptosis and autophagy induced cell death occur independently after siramesine and lapatinib treatment in breast cancer cells. PLoS One 2017 Aug 21;12(8): e0182921.
• Duncan J, Whittle M, Nakamura K, Abell AN, Midland AA, Zawistowski JS, et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple‐negative breast cancer. Cell 2012 Apr 13;149(2):307‐21.
• Li H, Yang P, Wang J, Zhang J, Ma Q, Jiang Y, Wu Y, Han T, Xiang D. HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. J Hematol Oncol. 2022 Jan 6;15(1):2.
• Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, et al. Caspase- independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res. 2013 Feb 15;19(4):845-54.
• Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM, Seashore-Ludlow B, et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 2017 Jul 27;547(7664):453–7.
• Hangauer MJ, Viswanathan VS, Ryan MJ, Bole D, Eaton JK, Matov A, et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 2017 Nov 9;551(7679):247–50.
• Saatci O, Alam R, Huynh-Dam KT, Isik A, Uner M, Belder N, et al. Targeting LINC00152 activates cAMP/Ca2+/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer. Cell Death Dis. 2024 Jun 15;15(6):418.
• Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci 2016 Mar; 41(3): 274–86.
• Pratt DA Tallman KA, Porter NA. Free radical oxidation of polyunsaturated lipids: new mechanistic insights and the development of peroxyl radical clocks. Acc Chem Res 2011 Jun 21;44(6): 458–67.
• Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE et al. Ferroptosis: an iron‐dependent form of nonapoptotic cell death. Cell 2012; May 25;149(5):1060-72.
• Stockwell BR, Friedmann Angeli JPF, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017 Oct 5;171(2):273-85.
• Vigil D, Cherfils J, Rossman KL, Der CJ. Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer 2010 Dec;10(12):842–57.
• Welinder C, Jönsson GB, Ingvar E, Lundgren L, Baldetorp B, Olsson H, et al. Analysis of alpha-synuclein in malignant melanoma- development of a SRM quantification assay. PLoS One 2014 Oct 21; 9(10): e110804.
• Huang P, Yang XD, Chen SD, Xiao Q. The association between Parkinson's disease and melanoma: a systematic review and meta-analysis. Transl Neurodegener 2015 Nov 3; 4:21.
• Bose A, Petsko GA, Eliezer D. Parkinson's disease and melanoma: co-occurrence and mechanisms. J Parkinsons Dis 2018;8(3):385-98.
• Yang, WS, Sriramaratnam, R, Welsch ME, Shimada K, Skouta R,Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 2014 Jan 16;156(1-2):317–31.
• Müller T, Dewitz C, Schmitz J, Schröder AS, Brasen JH, Stockwell BR, et al. Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cell. Mol. Life Sci 2017 Oct; 74(19):3631–45.
• Cheok CF, Verma CS, Baselga J, Lane DP. Translating p53 into the clinic. Nat. Rev. Clin. Oncol 2011 Jan; 8(1):25–37.
• Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 2015 Apr 2;520(7545):57–62.
• Chen X, Comish PB, Tang D, Kang R. Characteristics and biomarkers of ferroptosis. front. Cell Dev. Biol 2021 Jan 21; 9:637162.
• Bridges RJ, Natale NR, Patel SA. System Xc (-) cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol. 2012 Jan;165(1):20–34.
• Brigelius-Flohe R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta 2013 May;1830(5):3289–303.
• Qi X, Wan Z, Jiang B, Ouyang Y, Feng W, Zhu H, et al. Inducing ferroptosis has the potential to overcome therapy resistance in breast cancer. Front Immunol. 2022 Nov 24; 13:1038225.
• Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator GPX4 triggers acute renal failure in mice. Nat.Cell Biol 2014 Dec;16(12):1180–91.
• Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat. Cell Biol 2018 Oct;20(10):1181-92.
• Li Z, Chen L, Chen C, Zhou Y, Hu D, Yang J, et al. Targeting ferroptosis in breast cancer. Biomark Res. 2020 Nov 5;8(1):58.
• Hassannia B, Vandenabeele P, Berghe TV. Targeting ferroptosis to ıron out cancer. Cancer cell 2019 Jun 10;35(6):830–49.
• Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X. Ferroptosis is an autophagic cell death process. Cell Res 2016 Sep;26(9):1021–32.
• Ge A, He Q, Zhao D, Li Y, Chen J, Deng Y, et al. Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis. J Cell Mol Med. 2024 Jan;28(1): e18044.
• Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008 Mar;15(3):234–45.
• Mdkhana B, Zaher SM, Abdin SM, Omar HA. Tangeretin boosts anticancer activity of metformin in breast cancer cells via curbing the energy production. Phytomedicine 2021 Mar; 83:153470.
• Perou CM, Sorlie T, Eisen MB, Van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000 Aug 17;406(6797):747–52.
• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69–90.
• Andre F, Pusztai L. Molecular classification of breast cancer: Implications for selection of adjuvant chemotherapy. Nat Clin Pract Oncol 2006 Nov;3(11):621–32.
• Szakács G, Paterson, JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006 Mar;5(3):219-34.
• Stavrovskaya AA, Stromskaya TP. Transport proteins of the ABC familya and multidrug resistance of tumor cells. Biochemistry (Mosc) 2008 May;73(5):592-604.
• Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002 Jan;2(1):48-58.
• Chen J, Lu L, Feng Y, Wang H, Dai L, Li Y, et al. PKD2 mediates multi-drug resistance in breast cancer cells through modulation of P-glycoprotein expression. Cancer lett. 2011 Jan 1;300(1):48-56.
• Chen X, Comish PB, Tang D, Kang R. Characteristics and biomarkers of ferroptosis. front. Cell Dev Biol. 2021 Jan 21:9:637162.
• Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 2000 Oct;11(4):265-83.
• Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol 2017 Apr 1;35(10):1049-60.
• Fraguas-Sanchez AI, Martin-Sabroso C, Fernandez-Carballido A, Torres-Suarez AI. Current status of nanomedicine in the chemotherapy of breast cancer. Cancer Chemother Pharmacol 2019 Oct;84(4):689-706.
• Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem pharnacol 1999 Apr 1;57(7):727-41.
• Hrelia S, Fiorentini D, Maraldi T, Angeloni C, Bordoni A, Biagi PL, et al. Doxorubicin induces early lipid peroxidation associated with changes in glucose transport in cultured cardiomyocytes. Biochim Biophys Acta 2002 Dec 23;1567(1-2):150–6.
• Caetano-Pinto P, Jansen J, Assaraf YG, Masereeuw R. The importance of breast cancer resistance protein to the kidneys excretory function and chemotherapeutic resistance. Drug Resist Updat. 2017 Jan; 30:15-27.
• Sun D, Li YC, Zhang XY. Lidocaine promoted ferroptosis by targeting miR-382-5p/SLC7A11 axis in ovarian and breast Cancer. Front Pharmacol 2021 May 26; 12:681223.