이전|다음

중약 활성 성분에 의한 철사멸사 조절을 통한 유방암 항암 연구 진전

  • role： First author第一作者
  • Affiliation：

    The First Affiliated Hospital of Henan University of Chinese Medicine， Zhengzhou 450000，China

    The First Clinical Medical School， Henan University of Chinese Medicine， Zhengzhou 450000，China

  • Email：aurora9768@163.com
  • Introduction：刘妍，在读硕士，从事中医药防治女性生殖内分泌疾病研究，E-mail：aurora9768@163.com
LIU Yan12,  
  • Affiliation：

    The Second Clinical Medical School， Henan University of Chinese Medicine， Zhengzhou 450002，China

YANG Zhenyao3,  
  • Affiliation：

    The Second Clinical Medical School， Henan University of Chinese Medicine， Zhengzhou 450002，China

WANG Chengzhi3,  
  • role： Corresponding author通信作者
  • Affiliation：

    The First Affiliated Hospital of Henan University of Chinese Medicine， Zhengzhou 450000，China

  • Email：lijiuxian1982@163.com
  • Introduction：李久现，博士，副主任医师，从事中医药防治女性生殖内分泌疾病研究，E-mail：lijiuxian1982@163.com
LI Jiuxian1*

추상적인

유방암(BC)은 여성에게 흔한 악성 종양으로, 높은 발병률과 높은 사망률 등의 특징을 가지고 있어 여성 건강을 심각하게 위협합니다. 현재 BC에서 흔히 사용되는 치료법에는 수술, 방사선치료, 화학치료, 분자 표적치료, 내분비치료 등이 포함됩니다. 방사선치료와 화학치료는 종양 세포를 효과적으로 사멸시키고 증식과 분화를 억제할 수 있지만, 조혈 기능 장애, 면역 기능 저하 등의 부작용도 따릅니다. 기타 치료법 역시 내성, 재발률 증가, 삶의 질 저하, 임상 효과 미흡 등의 문제가 존재합니다. 따라서 더욱 효과적이고 독성이 낮은 신약 개발이 시급합니다. 철사멸사는 지질 과산화로 인해 발생하는 철 의존성 비아폽토시스성 프로그램화 세포사멸의 한 형태입니다. 최근 몇 년간 철사멸사는 종양 치료 분야에서 화두가 되었으며, BC 세포의 증식과 전이를 효과적으로 억제하고, BC의 항암제 내성을 개선하며, 방사선 치료에 대한 민감도를 향상시키는 것으로 점차 입증되고 있습니다. 중약은 다성분, 다표적, 부작용이 적다는 장점으로 BC 치료에 널리 사용되고 있습니다. 많은 연구에서 사포닌, 플라보노이드, 테르펜, 페놀, 다당류 등 중약의 활성 성분이 철 대사, 지질 대사, 글루타메이트/시스테인 역수송체(System Xc-)/글루타티온(GSH)/글루타티온 과산화효소4(GPX4) 관련 경로를 조절하여 BC 세포 내 지질 과산화 수준, 활성 산소(ROS), 말론디알데하이드(MDA), Fe2+ 함량을 증가시키고 BC 세포의 증식과 전이를 억제하는 것으로 나타났습니다. 따라서 본 논문에서는 최근 국내외 관련 문헌을 종합하여 철사멸사에 의한 BC 개입의 분자 기전과 중약 활성 성분의 철사멸사 표적 개입 연구 동향을 정리하여 BC 신약 개발에 대한 아이디어를 제공하고자 합니다.

키워드

유방암;철사멸사;중약 활성 성분;기전 연구

References

  1. 1.
    BRAY F，LAVERSANNE M，SUNG H，et al.Global cancer statistics 2022：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin，2024，74（3）：229-263.
  2. 2.
    SENKUS E，KYRIAKIDES S，OHNO S，et al.Primary breast cancer：ESMO Clinical Practice Guidelines for diagnosis，treatment and follow-up［J］.Ann Oncol，2015，26（suppl）：v8-v30.
  3. 3.
    STOCKWELL B R，FRIEDMANN ANGELI J P，BAYIR H，et al.Ferroptosis：A regulated cell death nexus linking metabolism，redox biology，and disease［J］.Cell，2017，171（2）：273-285.
  4. 4.
    SUI S Y，XU S P，PANG D.Emerging role of ferroptosis in breast cancer：New dawn for overcoming tumor progression［J］.Pharmacol Ther，2022，232：107992.
  5. 5.
    WEN X L，CAI F Y，CHENG B T，et al.Research progress on pharmacological mechanism of TCM in prevention and treatment of breast cancer［J］.Chin J Exp Tradit Med Form，2025，31（22）：252-263.
  6. 6.
    DIXON S J，LEMBERG K M，LAMPRECHT M R，et al.Ferroptosis：An iron-dependent form of nonapoptotic cell death［J］.Cell，2012，149（5）：1060-1072.
  7. 7.
    LI J，CAO F，YIN H L，et al.Ferroptosis：Past，present and future［J］.Cell Death Dis，2020，11（2）：88.
  8. 8.
    XIE Y，HOU W，SONG X，et al. Ferroptosis：Process and function［J］.Cell Death Differ，2016，23（3）：369-379.
  9. 9.
    FANG Y Y，CHEN X C，TAN Q Y，et al. Inhibiting ferroptosis through disrupting the NCOA4-FTH1 interaction：A new mechanism of action［J］.ACS Cent Sci，2021，7（6）：980-989.
  10. 10.
    MARTIN-PEREZ M，URDIROZ-URRICELQUI U，BIGAS C，et al.The role of lipids in cancer progression and metastasis［J］.Cell Metab，2022，34（11）：1675-1699.
  11. 11.
    CHEN C L，LIU P，DUAN X Y，et al.Deferoxamine-induced high expression of TfR1 and DMT1 enhanced iron uptake in triple-negative breast cancer cells by activating IL-6/PI3K/Akt pathway［J］.Onco Targets Ther，2019：4359-4377.
  12. 12.
    YU H C，YANG C C，JIAN L，et al.Sulfasalazine-induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor［J］.Oncol Rep，2019，42（2）：826-838.
  13. 13.
    OZKAN E，BAKAR-ATES F.Etoposide in combination with erastin synergistically altered iron homeostasis and induced ferroptotic cell death through regulating IREB2/FPN1 expression in estrogen receptor positive-breast cancer cells［J］.Life Sci，2023，312：121222.
  14. 14.
    HUANG G Q，CAI Y W，REN M H，et al.Salidroside sensitizes triple-negative breast cancer to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy［J］.J Adv Res，2024，74：589-607.
  15. 15.
    CHEN X，KANG R，KROEMER G，et al.Broadening horizons：The role of ferroptosis in cancer［J］.Nat Rev Clin Oncol，2021，18（5）：280-296.
  16. 16.
    DOLL S，PRONETH B，TYURINA Y Y，et al.ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition［J］.Nat Chem Biol，2017，13（1）：91-98.
  17. 17.
    ZHANG H L，HU B X，LI Z L，et al.PKCβⅡ phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis［J］.Nat Cell Biol，2022，24（1）：88-98.
  18. 18.
    WU X H，LIU C L，LI Z，et al.Regulation of GSK3β/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer［J］.Mol Cell Biochem，2020，473（1）：217-228.
  19. 19.
    XIE Y，ZHOU X，LI J，et al.Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway［J］.Bioorg Chem，2021，109：104744.
  20. 20.
    PARKER J L，DEME J C，KOLOKOURIS D，et al.Molecular basis for redox control by the human cystine/glutamate antiporter system xc［J］.Nat Commun，2021，12（1）：7147.
  21. 21.
    DORNIER E，RABAS N，MITCHELL L，et al.Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells［J］.Nat Commun，2017，8（1）：2255.
  22. 22.
    ZENG C，LIN J，ZHANG K T，et al.SHARPIN promotes cell proliferation of cholangiocarcinoma and inhibits ferroptosis via p53/SLC7A11/GPX4 signaling［J］.Cancer Sci，2022，113（11）：3766-3775.
  23. 23.
    UNGERLEIDER N A，RAO S G，SHAHBANDI A，et al.Breast cancer survival predicted by TP53 mutation status differs markedly depending on treatment［J］.Breast Cancer Res，2018，20：1-8.
  24. 24.
    SYNNOTT N C，BAUER M R，MADDEN S，et al.Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer：Preclinical investigation with the anti-p53 drug，PK11007［J］.Cancer Lett，2018，414：99-106.
  25. 25.
    MAO C，WANG X，LIU Y T，et al.A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53［J］.Cancer Res，2018，78（13）：3484-3496.
  26. 26.
    YADAV P，SHARMA P，SUNDARAM S，et al.SLC7A11/xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells［J］.Cancer Lett，2021，522：211-224.
  27. 27.
    PEI J，PAN X Y，WEI G H，et al.Research progress of glutathione peroxidase family （GPX） in redoxidation［J］.Front Pharmacol，2023，14：1147414.
  28. 28.
    TIAN Y H，LYU J，TAN Z H，et al.Expression and prognostic value of GPX4 and FOXP2 in breast cancer［J］.Chin J Birth Health Hered，2023，31（9）：1848-1852.
  29. 29.
    ZHANG X F，SUI S Y，WANG L L，et al.Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin［J］.J Cell Physiol，2020，235（4）：3425-3437.
  30. 30.
    HOU Y F，CAI S，YU S Y，et al.Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer［J］.Acta Biochim Biophys Sin，2021，53（3）：333-341.
  31. 31.
    ANANDHAN A，DODSON M，SCHMIDLIN C J，et al.Breakdown of an ironclad defense system：The critical role of NRF2 in mediating ferroptosis［J］.Cell Chem Biol，2020，27（4）：436-447.
  32. 32.
    LI X，SU X H，ZENG J，et al.The novel inhibitor of STARD7 induces ferroptosis through the Nrf2/EGR1 pathway in TNBC［J］.J Med Res Combat Trauma Care，2024，37（5）：462-471.
  33. 33.
    LI X，LI D H，GAO X M，et al.Studies on Paris saponin promoting iron death in triple negative breast cancer cells through p53/SLC7A11 signal axis［J］.Med J Chin PLA，2023，48（1）：58-63.
  34. 34.
    ZHOU Y L，YANG J J，CHEN C，et al.Polyphyllin Ⅲ-induced ferroptosis in MDA-MB-231 triple-negative breast cancer cells can be protected against by KLF4-mediated upregulation of xCT［J］.Front Pharmacol，2021，12：670224.
  35. 35.
    ZHANG Y B，ZHANG H Z，RUAN Y D，et al.Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells［J］.Chin J Chin Mater Med，2024，49（9）：2385-2392.
  36. 36.
    ZHANG J.Mechanism of salidroside inducing ferroptosis in breast cancer cells［D］.Tangshan：North China University of Science and Technology，2023.
  37. 37.
    CHEN H C，TANG H H，HSU W H，et al.Vulnerability of triple-negative breast cancer to saponin formosanin C-induced ferroptosis［J］.Antioxidants （Basel），2022，11（2）：298.
  38. 38.
    AN S B，HU M Y.Quercetin promotes TFEB nuclear translocation and activates lysosomal degradation of ferritin to induce ferroptosis in breast cancer cells［J］.Comput Intell Neurosci，2022，2022（1）：5299218.
  39. 39.
    NIU X M，DING X H，TONG Q，et al.Myricetin inhibits 4T1 breast tumor growth in mice via induction of Nrf-2/GPX4 pathway-mediated ferroptosis［J］.Toxicol Appl Pharmacol，2024，488：116990.
  40. 40.
    WANG J G，LI Y，ZHANG J，et al.Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancer［J］.Immunopharmacol Immunotoxicol，2023，45（4）：443-454.
  41. 41.
    HE D，TAN X N，LI L P，et al.Brazilin actuates ferroptosis in breast cancer cells via p53/SLC7A11/GPX4 signaling pathway［J］.Chin J Integr Med，2024，30（11）：1001-1006.
  42. 42.
    LI Z，WU X H，WANG W Y，et al.Fe（Ⅱ） and tannic acid-cloaked MOF as carrier of artemisinin for supply of ferrous ions to enhance treatment of triple-negative breast cancer［J］.Nanoscale Res Lett，2021，16（1）：37.
  43. 43.
    YIN L X，MA Y H，ZHANG H Y，et al.Mechanism of ferroptosis induced via hinokitiol iron chelate in breast cancer cells［J］.Sci Sin Vitae，2023，53（11）：1673-1684.
  44. 44.
    YE S Y，HU X Y，SUN S W，et al.Oridonin promotes RSL3-induced ferroptosis in breast cancer cells by regulating the oxidative stress signaling pathway JNK/Nrf2/HO-1［J］.Eur J Pharmacol，2024，974：176620.
  45. 45.
    LIN Y S，SHEN Y C，WU C Y，et al.Danshen improves survival of patients with breast cancer and dihydroisotanshinone Ⅰ induces ferroptosis and apoptosis of breast cancer cells［J］.Front Pharmacol，2019，10：1226.
  46. 46.
    YAN L.Cryptotanshinone suppresses triple-negative breast cancer via ferroptosis［D］.Shanghai：Naval Medical University，2021.
  47. 47.
    WEN W，JIN K，CHE Y，et al.Arnicolide D inhibits oxidative stress-induced breast cancer cell growth and invasion through apoptosis，ferroptosis，and parthanatos［J］.Anticancer Agents Med Chem，2024，24（11）：836-844.
  48. 48.
    DING Y H，CHEN X P，LIU C，et al.Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells［J］.J Hematol Oncol，2021，14（1）：19.
  49. 49.
    RUAN Y D，ZHANG H Z，HUANG H T，et al.Role and mechanism of Cucurbitacin B in suppressing proliferation of breast cancer 4T1 cells via inducing ferroptosis［J］.Chin J Exp Tradit Med Form，2025，31（7）：91-97.
  50. 50.
    ZHAO P，SONG H，GAO F T，et al.A novel derivative of curcumol，HCL-23，inhibits the malignant phenotype of triple-negative breast cancer and induces apoptosis and HO-1-dependent ferroptosis［J］.Molecules，2023，28（8）：3389.
  51. 51.
    WEI Y Y，ZHU Z H，HU H T，et al.Eupaformosanin induces apoptosis and ferroptosis through ubiquitination of mutant p53 in triple-negative breast cancer［J］.Eur J Pharmacol，2022，924：174970.
  52. 52.
    WEN Y，CHEN H S，ZHANG L，et al.Glycyrrhetinic acid induces oxidative/nitrative stress and drives ferroptosis through activating NADPH oxidases and iNOS，and depriving glutathione in triple-negative breast cancer cells［J］.Free Radic Biol Med，2021，173：41-51.
  53. 53.
    LI R H，ZHANG J，ZHOU Y F，et al.Transcriptome investigation and in vitro verification of curcumin‐induced HO‐1 as a feature of ferroptosis in breast cancer cells［J］.Oxid Med Cell Longev，2020，2020（1）：3469840.
  54. 54.
    CAO X L，LI Y，WANG Y B，et al.Curcumin suppresses tumorigenesis by ferroptosis in breast cancer［J］.PLoS One，2022，17（1）：e0261370.
  55. 55.
    KHORSANDI K，KIANMEHR Z，HOSSEINMARDI Z，et al.Anti-cancer effect of gallic acid in presence of low level laser irradiation：ROS production and induction of apoptosis and ferroptosis［J］.Cancer Cell Int，2020，20：1-14.
  56. 56.
    CHOI Y，PARK S，LEE S，et al.Cremastranone-derived homoisoflavanes suppress the growth of breast cancer cells via cell cycle arrest and caspase-independent cell death［J］.Biomol Ther （Seoul），2023，31（5）：526-535.
  57. 57.
    DU X，ZHANG J J，LIU L，et al.A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells［J］.J Zhejiang Univ Sci B，2022，23（4）：286-299.
  58. 58.
    ZHAI F G，LIANG Q C，WU Y Y，et al.Red ginseng polysaccharide exhibits anticancer activity through GPX4 downregulation-induced ferroptosis［J］.Pharm Biol，2022，60（1）：909-914.
  59. 59.
    JING S W，LU Y T，ZHANG J，et al.Levistilide a induces ferroptosis by activating the Nrf2/HO-1 signaling pathway in breast cancer cells［J］.Drug Des Dev Ther，2022，16：2981-2993.
  60. 60.
    HE D，LI L P，TAN X N，Mechanism of esculetin promoting ferroptosis of mouse breast cancer 4T1 cells based on p53/SLC7A11/GPX4 axis［J］.Chin J Pathophysiol，2024，40（2）：282-290.
  61. 61.
    ZHANG J，GAO R F，LI J，et al.Alloimperatorin activates apoptosis，ferroptosis，and oxeiptosis to inhibit the growth and invasion of breast cancer cells in vitro［J］.Biochem Cell Biol，2022，100（3）：213-222.
  62. 62.
    YIN J M，LIN Y J，FANG W W，et al.Tetrandrine citrate suppresses breast cancer via depletion of glutathione peroxidase 4 and activation of nuclear receptor coactivator 4-mediated ferritinophagy［J］.Front Pharmacol，2022，13：820593.
  63. 63.
    BEATTY A，SINGH T，TYURINA Y Y，et al.Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1［J］.Nat Commun，2021，12（1）：2244.
  64. 64.
    KUANG X P.Study on the anti-breast cancer effect and mechanism of indirubin obtained from Indigo naturalis［D］.Kunming：Yunnan University of Chinese Medicine，2021.

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