摘要
现代药理学研究表明，异硫氰酸酯家族（ITCs）作为抗癌剂具有巨大潜力。ITCs可以通过调节涉及致癌物生物转化和解毒、炎症、细胞周期、细胞凋亡和表观遗传调控的多种信号通路来抑制癌变并抑制肿瘤生长。萝卜硫素作为ITCs的成员之一，具有许多预防癌症的特性，它能促进程序性细胞死亡/凋亡、诱导细胞周期停滞、抑制血管生成、抗炎、降低对致癌物的易感性、减少肿瘤细胞侵袭和转移，并表现出抗氧化和抗炎特性。近年来四大常见的女性恶性肿瘤乳腺癌、宫颈癌、子宫内膜癌、卵巢癌发病率较前上升，严重危害着女性的身心健康。而萝卜硫素在此范围内研究较少，因此，本篇综述通过介绍萝卜硫素在乳腺癌、宫颈癌、子宫内膜癌、卵巢癌中的作用及可能机制，以期为女性恶性肿瘤的临床治疗提供新线索。
关键词： 萝卜硫素；异硫氰酸酯；乳腺癌；宫颈癌；子宫内膜癌；卵巢癌
Abstract
Modern pharmacological studies have shown that the Isothiocyanate family(ITCs) has great potential as anticancer agents. ITCs can inhibit carcinogenesis and inhibit tumor growth by regulating multiple signaling pathways involved in carcinogenic biotransformation and detoxification, inflammation, cell cycle, apoptosis, and epigenetic regulation. Sulforaphane, as a member of the Isothiocyanate family, has many cancer-preventing properties, it promotes programmed cell death/apoptosis, induces cell cycle arrest, inhibits angiogenesis, is anti-inflammatory, reduces susceptibility to carcinogens, reduces tumor cell invasion and metastasis, and exhibits antioxidant and anti-inflammatory properties. In recent years, the incidence of four common female malignant tumors, breast cancer, cervical cancer, endometrial cancer and ovarian cancer, has increased, seriously endangering the physical and mental health of women. However, there are few researches on sulforaphane in this scope. Therefore, this review introduces the role and possible mechanism of sulforaphane in breast cancer, cervical cancer, endometrial cancer and ovarian cancer, hoping to provide new clues for the clinical treatment of female malignant tumors.
Key words： Sulforaphane; Isothiocyanate; Breast cancer; Cervical cancer; Endometrial cancer; Ovarian cancer
参考文献 References
[1] Wang X,Yan Y,Chen X, et al. The Antitumor Activities of Marsdenia Tenacissima[J]. Frontiers in Oncology, 2018, 8: 473.
[2] Henry ML,Niu J,Zhang N, et al. Cardiotoxicity and Cardiac Monitoring Among Chemotherapy-treated Breast~cancer Patients[J]. JACC Cardiovascular Imaging, 2018, 11(8): 1084-1093.
[3] Zhi X,Zhang Y,Huang J, et al. Seven-membered Lactam Derivatives of Podophyllotoxins as New Pesticidal Agents[J]. Scientific Reports, 2017, 7(1): 3917.
[4] Janczewski Ł. Sulforaphane and Its Bifunctional Analogs: Synthesis and Biological Activity[J]. Molecules, 2022, 27(5) :1750.
[5] Wu G,Yan Y,Zhou Y, et al. Sulforaphane: Expected to Become a Novel Antitumor Compound[J]. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 2020, 28(4): 439-446.
[6] Kaiser AE,Baniasadi M,Giansiracusa D, et al. Sulforaphane: a Broccoli Bioactive Phytocompound with Cancer Preventive Potential[J]. Cancers, 2021, 13(19) :4796.
[7] Rai Rajani,Essel Kathleen-Gong,Benbrook Doris-Mangiaracina, et al. Preclinical Efficacy and Involvement of AKT, mTOR, and ERK Kinases in the Mechanism of Sulforaphane against Endometrial Cancer[Z]. Cancers (Basel), 2020;12(5):1273.
[8] Nandini D,Rao R,Deepak B, et al. Sulforaphane in Broccoli: the Green Chemoprevention!! Role in Cancer Prevention and Therapy[J]. Journal of Oral and Maxillofacial Pathology, 2020, 24(2): 405.
[9] Jackson Steven-J-T,Singletary Keith-W. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization[Z]. J Nutr, 2004;134(9):2229-2236.
[10] Cao C,Wu H,Vasilatos SN, et al. HDAC5-LSD1 Axis Regulates Antineoplastic Effect of Natural HDAC Inhibitor Sulforaphane in Human Breast Cancer Cells[J]. International Journal of Cancer, 2018, 143(6): 1388-1401.
[11] Yang F,Wang F,Liu Y, et al. Sulforaphane Induces Autophagy By Inhibition of HDAC6-mediated PTEN Activation in Triple Negative Breast Cancer Cells[J]. Life Sciences, 2018, 213: 149-157.
[12] Yang M,Teng W,Qu Y, et al. Sulforaphene Inhibits Triple Negative Breast Cancer Through Activating Tumor Suppressor Egr1[J]. Breast Cancer Research and Treatment, 2016, 158(2): 86-277.
[13] Cheng A,Shen C,Hung C, et al. Sulforaphane Decrease of SERTAD1 Expression Triggers G1/S Arrest in Breast Cancer Cells[J]. Journal of Medicinal Food, 2019, 22(5): 444-450.
[14] Wang S,Wang Y,Liu X, et al. SFN Enhanced the Radiosensitivity of Cervical Cancer Cells Via Activating LATS2 and Blocking Rad51/MDC1 Recruitment to NDA Damage Site[J]. Cancers, 2022, 14(8).
[15] Sharma Chhavi,Sadrieh Lida,Priyani Anita, et al. Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells[Z]. Cancer Epidemiol, 2011;35(3):272-278.
[16] Khan Munawwar-Ali,Sundaram Madhumitha-Kedhari, Hamza Amina, et al. Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells[Z]. Evid Based Complement Alternat Med, 2015: 412149.
[17] Cheng Ya-Min, Tsai Ching-Chou, Hsu Yi-Chiang. Sulforaphane, a Dietary Isothiocyanate, Induces G₂/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association[Z]. Int J Mol Sci, 2016;17(9):1530.
[18] Kan Shi-Feng,Wang Jian,Sun Guan-Xing. Sulforaphane regulates apoptosis- and proliferation‑related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer[Z]. Int J Mol Med, 2018: 2447-2458.
[19] Tian Miao,Tian Dan,Qiao Xiaofang, et al. Modulation of Myb-induced NF-kB -STAT3 signaling and resulting cisplatin resistance in ovarian cancer by dietary factors[Z], J Cell Physiol, 2019;234(11):21126-21134., 2019: 21126-21134.
[20] Gong T,Liu X,Zhan Z, et al. Sulforaphane Enhances the Cisplatin Sensitivity Through Regulating DNA Repair and Accumulation of Intracellular Cisplatin in Ovarian Cancer Cells[J]. Experimental Cell Research, 2020, 393(2): 112061.