白头翁皂苷及其单体抗肿瘤作用及机制的研究进展

doi:10.5246/jcps.2021.05.030

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (5): 381-392.DOI: 10.5246/jcps.2021.05.030

白头翁皂苷及其单体抗肿瘤作用及机制的研究进展

宋慧慧¹^,², 向卓², 薛淑一³, 苗青², 赵丽艳², 李明春²^,^*()

1. 大连医科大学药学院, 辽宁大连 116000
2. 中国人民解放军海军第九七一医院药剂科, 山东青岛 266071
3. 青岛市中心医院药学部, 山东青岛 266042

收稿日期:2020-09-18 修回日期:2020-11-15 接受日期:2020-12-30 出版日期:2021-05-31 发布日期:2021-05-29
通讯作者: 李明春
作者简介:
+ Tel.: +86-532-51870518, E-mail: lmc401y@163.com
基金资助:
The National Natural Science Foundation of China (Grant No. 81703768?and?81803400), and the Natural Science Foundation of Shandong Province (Grant No. ZR2017MH118 and ZR2018BH045).

Advances in anti-tumor effects and mechanisms of Pulsatilla Chinensis saponins and its monomers

Huihui Song¹^,², Zhuo Xiang², Shuyi Xue³, Qing Miao², Liyan Zhao², Mingchun Li²^,^*()

1 College of Pharmacy, Dalian Medical University, Dalian 116000, China
2 Department of Pharmacy, Hospital 971 of Chinese People’s Liberation Army, Qingdao 266071, China
3 Department of Pharmacy, Qingdao Central Hospital, Qingdao 266042, China

Received:2020-09-18 Revised:2020-11-15 Accepted:2020-12-30 Online:2021-05-31 Published:2021-05-29
Contact: Mingchun Li

摘要/Abstract

摘要：

白头翁是我国中医中一味传统的中药材, 广泛应用于中医临床。近年来的医学研究发现, 从白头翁中提取的天然产物白头翁皂苷及其单体化合物具有多种生物活性, 尤其是从中分离得到的三萜类皂苷, 具有显著且广谱的抗肿瘤作用, 其潜在抗肿瘤分子机制包括抑制肿瘤细胞的生长和增殖、抑制肿瘤细胞的迁移、侵袭和转移、阻滞肿瘤细胞周期、调控癌细胞能量代谢、抗肿瘤血管生成、诱导癌细胞分化、凋亡和自噬、逆转癌细胞耐药、调节多种相关信号通路及改善肿瘤细胞的炎症微环境等。本文对白头翁皂苷及其单体在不同肿瘤中的相关抗癌机制进行综述, 旨在为白头翁及其单体的抗肿瘤新药研发及临床应用提供理论基础。

关键词: 白头翁, 白头翁皂苷, 单体, 抗肿瘤作用, 分子机制

Abstract:

As a traditional Chinese herbal medicine, Pulsatilla Chinensis (P. Chinensis) is widely used in the clinical practice of traditional Chinese medicine (TCM). Recently, medical research has found that the natural product P. Chinensis saponins and their monomeric compounds extracted from P. Chinensis have a variety of biological activities, especially the triterpenoid saponins, which have significant and broad-spectrum anti-tumor effects. Moreover, its anti-tumor molecular mechanisms include inhibition of the growth and proliferation of tumor cells, repression of the migration, invasion, and metastasis, prevention of tumor cell cycle, regulation of cancer cell energy metabolism, anti-tumor angiogenesis, induction of cancer cell differentiation, apoptosis and autophagy, reversing cancer cell resistance, regulation a variety of related signaling pathways, and improvement of the inflammatory microenvironment of tumor cells. In the present work, we reviewed the related anticancer mechanisms of P. Chinensis saponins and their monomers in different tumors, aiming to provide a theoretical basis for the development and clinical application of new anti-tumor drugs of P. Chinensis saponins and their monomeric compounds.

Key words: Pulsatilla Chinensis, Pulsatilla Chinensis saponins, Monomer, Anti-tumor effect, Molecular mechanism

Supporting:

宋慧慧, 向卓, 薛淑一, 苗青, 赵丽艳, 李明春. 白头翁皂苷及其单体抗肿瘤作用及机制的研究进展[J]. 中国药学(英文版), 2021, 30(5): 381-392.

Huihui Song, Zhuo Xiang, Shuyi Xue, Qing Miao, Liyan Zhao, Mingchun Li. Advances in anti-tumor effects and mechanisms of Pulsatilla Chinensis saponins and its monomers[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(5): 381-392.

图/表 1

参考文献 52

[1]	Chen, W.Q.; Zheng, R.S.; Baade, P.D.; Zhang, S.W.; Zeng, H.M.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin. 2016, 66, 115–132.
[2]	Tong, X.H.; Han, L.; Duan, H.Q.; Cui, Y.R.; Feng, Y.L.; Zhu, Y.M.; Chen, Z.; Yang, S.L. The derivatives of Pulsatilla saponin A, a bioactive compound from Pulsatilla chinensis: Their synthesis, cytotoxicity, haemolytic toxicity and mechanism of action. Eur. J. Med. Chem. 2017, 129, 325–336.
[3]	Guo, X.Z.; Xie, Y.; Lian, S.; Li, Z.X.; Gao, Y.; Xu, Z.; Hu, P.; Chen, M.C.; Sun, Z.L.; Tian, X.T.; Huang, C.G. A sensitive HPLC-MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23-hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins. Biomed. Chromatogr. 2018, 32, e4124.
[4]	Zheng, Y.T.; Zhou, F.; Wu, X.L.; Wen, X.Z.; Li, Y.N.; Yan, B.; Zhang, J.W.; Hao, G.; Ye, W.C.; Wang, G.J. 23-Hydroxybetulinic acid from Pulsatilla chinensis (Bunge) Regel synergizes the antitumor activities of doxorubicin in vitro and in vivo. J. Ethnopharmacol. 2010, 128, 615–622.
[5]	Liang, Y.C.; Xu, X.J.; Yu, H.M.; Li, L.; Hong, T.; Ji, Q.B.; Feng, Y.L.; Jin, S.; Song, Y.Q.; Guo, J.; Zheng, Z.B.; Ye, Q.N.; Yang, S.L. Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis. Tumor Biol. 2016, 37, 9837–9847.
[6]	Liu, M.; Zhao, X.Z.; Xiao, L.; Liu, G.; Liu, H.Z.; Wang, X.Y.; Feng, X.; Lin, X.K. Cytotoxicity of the compounds isolated from Pulsatilla chinensis saponins and apoptosis induced by 23-hydroxybetulinic acid. Pharm. Biol. 2015, 53, 1–9.
[7]	Duan, Y.S.; Zhang, S.; Wang, L.L.; Zhou, X.; He, Q.H.; Liu, S.; Yue, K.; Wang, X.D. Targeted silencing of CXCR4 inhibits epithelial-mesenchymal transition in oral squamous cell carcinoma. Oncol. Lett. 2016, 12, 2055–2061.
[8]	Pan, W.J.; Ding, L. Effects of Pulchinenoside at Different Concentrations on the Proliferation and Migration of Squamous Cell carcinoma cells and calpain-1, E-cadherin and N-cadherin protein. China Pharmacist. 2018, 21, 984–988.
[9]	Goode, E.; Smyth, E. Immunotherapy for gastroesophageal cancer. J. Clin. Med. 2016, 5, 84.
[10]	Guan, Z.Y.; Chen, L.Y.; Luo, Y.Y.; Cui, Y.R.; Shou, B.Y.; Zhou, L.F. Effect of Saponins in Pulsatillae Radix on Proliferation and Apoptosis of NCI-H460 Lung Cancer Cells and Screening of its Differentially Expressed Proteins. Chin. J. Exp. Med. Formul. 2019, 25, 49–56.
[11]	Luo, Y.Y. Ph.D. thesis, Hunan University of Traditional Chinese Medicine. 2014.
[12]	Yang, H.; Kim, H.; Kim, Y.C.; Sung, S.H. Cytotoxic activities of naturally occurring oleanane-, ursane-, and lupane-type triterpenes on HepG2 and AGS cells. Pharmacogn. Mag. 2017, 13, 118.
[13]	Hong, S.W.; Jung, K.H.; Lee, H.S.; Son, M.K.; Yan, H.H.; Kang, N.S.; Lee, J.; Hong, S.S. SB365, Pulsatilla saponin D, targets c-Met and exerts antiangiogenic and antitumor activities. Carcinogenesis. 2013, 34, 2156–2169.
[14]	Luo, Y.Y.; Yan, X.; Xie, X.X.; Wang, M.L.; Feng, Y.L.; Yang, S.L.; Li, J. Study on Antitumor Effect and Its Structure-Activity Relationship of Pulsatilla Saponin and Its Major Constituents. Mod. Chin. Med. 2018, 20, 791–796.
[15]	Liang, C.Y. Ph.D. thesis, Beijing University of Traditional Chinese Medicine. 2016.
[16]	Chen, L.Y.; Zhou, M.J.; Cui, Y.R.; Wang, H.L.; Guan, Z.Y.; Luo, Y.Y. Effect of Pulsatilla saponins on Glycolysis Pathway Inhibiting Proliferation of Colorectal Cancer Cells in SW480. J. Chin. Med. Materls. 2019, 42, 652–656.
[17]	Cui, Y.R.; Wang, H.L.; Chen, L.Y.; Guan, Z.Y.; Luo, Y.Y. Effects of Pulsatilla Saponin A on key proteins and regulatory factor HIF-1α of glycolytic pathway in SW480 human colorectal cancer cells. Chin. Tradit. Patent Med. 2019, 41, 2887–2892.
[18]	Li, M.; Fang, M.Z. Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism. China Oncol. 2015, 25, 38–44.
[19]	Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424.
[20]	Luo, Y.Y.; Chen, L.Y.; Jian, H.; Cui, Y.R.; Xie, X.X.; Liu, P.; Yang, S.L.; Guo, J.S. Regulation of saponins from Pulsatilla chinensis on energy metabolism of Bel-7402 xenograft in nude mice. Chin. Tradit. Herb Drug. 2014, 45, 973–977.
[21]	Liu, Q.; Chen, W.C.; Jiao, Y.; Hou, J.Q.; Wu, Q.Y.; Liu, Y.L.; Qi, X.F. Pulsatilla saponin A, an active molecule from Pulsatilla chinensis, induces cancer cell death and inhibits tumor growth in mouse xenograft models. J. Surg. Res. 2014, 188, 387–395.
[22]	Xue, S.Y.; Zhou, Y.; Zhang, J.; Xiang, Z.; Liu, Y.; Miao, T.; Liu, G.X.; Liu, B.G.; Liu, X.; Shen, L.X.; Zhang, Z.; Li, M.C.; Miao, Q. Anemoside B4 exerts anti-cancer effect by inducing apoptosis and autophagy through inhibiton of PI3K/Akt/mTOR pathway in hepatocellular carcinoma. Am. J. Transl. Res. 2019, 11, 2580–2589.
[23]	Xue, S.Y.; Li, M.C.; Miao, Q.; Zhou, Y. Inhibitory Effects and Mechanism of Anemoside B4 on Hepatocellular Carcinoma Huh-7 Cells and Tumorbearing Nude Mice. China Pharm. 2019, 30, 601–607.
[24]	Hong, S.W.; Jung, K.H.; Lee, H.S.; Choi, M.J.; Son, M.K.; Zheng, H.M.; Hong, S.S. SB365 inhibits angiogenesis and induces apoptosis of hepatocellular carcinoma through modulation of PI₃K/Akt/mTOR signaling pathway. Cancer Sci. 2012, 103, 1929–1937.
[25]	Xu, K.; Shu, Z.; Wang, Y.L.; Xu, Q.M.; Yang, S.L.; liu, Y.L. Effect of Pulsatilla saponin D on hepatocarcinoma in vivo and in vitro. Chin. Tradit. Patent Med. 2014, 36, 240–244.
[26]	Yue, W.H.; Xu, K.; Feng, Y.L.; Zhang, T.; Xu, Q.M.; Yang, S.L.; Liu, Y.L. Antihepatocarcinoma effect in vitro of pulchinenoside D and mechanisms. Chin. Tradit. Herb Drug. 2014, 45, 3295–3301.
[27]	Lei, Y.H. M.S. thesis, Jinan University. 2017.
[28]	Wang, T.; Zhang, R.; Qi, X.F.; Bai, S.S.; Gong, F.; Chen, Z.X.; Cen, J.N.; Zhu, M.Q.; Dai, L. Differentiation of K562 cells induced by pulsatilla saponin A into erythroid lineage. Chin. J. Exp. Hematol. 2016, 24, 975–979.
[29]	Wang, T. M.S. thesis, Suzhou University. 2015.
[30]	Wang, T.; Gong, F.; Zhang, R.; Cen, J.N.; Dai, L.; Zhu, M.Q.; Qi, X.F. Pulsatilla saponin A induces differentiation in acute myeloid leukemia in vitro. Hematology. 2016, 21, 182–186.
[31]	Zhang, Y.L.; Bao, J.; Wang, K.; Jia, X.; Zhang, C.; Huang, B.R.; Chen, M.; Wan, J.; Su, H.; Wang, Y.; He, C. Pulsatilla saponin D inhibits autophagic flux and synergistically enhances the anticancer activity of chemotherapeutic agents against HeLa cells. Am. J. Chin. Med. 2015, 43, 1657–1670
[32]	Shain, K.H.; Dalton, W.S.; Tao, J. The tumor microenvironment shapes hallmarks of mature B-cell malignancies. Oncogene. 2015, 34, 4673–4682.
[33]	Zhou, Y.Y. M.S. Thesis, Suzhou University. 2017.
[34]	Mikawa, T.; LLeonart, M.E.; Takaori-Kondo, A.; Inagaki, N.; Yokode, M.; Kondoh, H. Dysregulated glycolysis as an oncogenic event. Cell Mol. Life Sci. 2015, 72, 1881–1892.
[35]	Lim, M.C.; Lee, M.; Shim, S.H.; Nam, E.J.; Lee, J.Y.; Kim, H.J.; Lee, Y.Y.; Lee, K.B.; Park, J.Y.; Kim, Y.H.; Ki, K.D.; Song, Y.J.; Chung, H.H.; Kim, S.; Lee, J.W.; Kim, J.W.; Bae, D.S.; Lee, J.M. Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement. J. Gynecol. Oncol. 2017, 28, e22.
[36]	Bhatla, N.; Aoki, D.; Sharma, D.N.; Sankaranarayanan, R. Cancer of the cervix uteri. Int. J. Gynecol. Obstet. 2018, 143, 22–36.
[37]	Wang, B.; Chen, W.; Zhang, X.Y.; Yin, L.L. Antiproliferative effect of pulsatilla saponin D on cervical cancer cells and its relationship with Wnt signaling pathway. Chin. J. Clin. Pharmacol. 2019, 35, 2732–2735.
[38]	Ren, N.N.; Duan, H.X.; Zhang, J.B. Study on Notch signaling pathway for mediating anti-cervical cancer effect of Anemoside B4 and its mechanism. Chongqing Med. J. 2020, 49, 705–708.
[39]	Siegel, R.L.; Fedewa, S.A.; Miller, K.D.; Goding-Sauer, A.; Pinheiro, P.S.; Martinez-Tyson, D.; Jemal, A. Cancer statistics for hispanics/latinos, 2015. CA Cancer J. Clin. 2015, 65, 457–480.
[40]	Wang, Y.E.; Yue, W.H.; Xu, Q.M.; Li, X.R.; Li, K.P. Antitumor effect and mechanism of pulchinenoside D on A549 tumor cells in vitro. J. Guangdong Pharm. Univ. 2018, 34, 316–319.
[41]	Jang, W.J.; Park, B.; Jeong, G.S.; Hong, S.S.; Jeong, C.H. SB365, Pulsatilla saponin D, suppresses the growth of gefitinib-resistant NSCLC cells with Met amplification. Oncol. Rep. 2014, 32, 2612–2618.
[42]	Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2017. CA Cancer J. Clin. 2017, 67, 7–30.
[43]	Liang, Y.C.; Xu, X.J.; Yu, H.M.; Li, L.; Hong, T.; Ji, Q.B.; Feng, Y.L.; Jin, S.; Song, Y.Q.; Guo, J.; Zheng, Z.B.; Ye, Q.N.; Yang, S.L. Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis. Tumor Biol. 2016, 37, 9837–9847.
[44]	Feng, X.L.; Liu, D. Effect of pulchinenoside D on the Wnt/β-catenin signaling pathway in human breast carcinoma cell lines MCF-7. J. Southeast Univ. 2017, 36, 379–383.
[45]	Hu, C.; Yue, W.H.; Peng, C.P.; Xu, Q.M.; Li, X.R.; Yang, S.L.; Wang, Y.L.; Liu, Y.L. Antitumor Effects of Pulsatilla Saponin D on MCF-7 Tumor Cells in Vitro and in Vivo. Tradit. Chin. Drug Res.Clin. Pharmacol. 2017, 28, 418–423.
[46]	Zou, X.J.; Hao, Y.Y.; Hu, Y.D.; Xie, M.X.; Bai, W. Pulsatilla saponin A affects proliferation and radiosensitivity of breast cancer cells by regulating miR-24-3p/RNF2 expression. Chin. J. Pathophysiol. 2020, 36, 865–870.
[47]	Yan, J.; Xu, C.H.; Li, Y.P.; Tang, B.; Xie, S.H.; Hong, T.; Zeng, E.M. Long non-coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL. J. Cell Mol. Med. 2019, 23, 5518–5531.
[48]	Peng, C.P.; Xu, Q.M.; Zhan, T. Li, X.R.; Yang, S.L.; Zhou,Y.; Liu, Y.L. Anti-glioma Effect and Mechanism of Alkali Hydrolysate of Total Saponins from Pulsatilla chinensis on Human Glioma U251 Cells. Tradit. Chin. Drug Res. Clin. Pharmacol. 2014, 25, 254–259.
[49]	Li, B.; Wang, Y.G.; Li, J.; Tang, H.F.; Chen, G. Pulsatilla saponin D induces cell apoptosis in the U87MG cells. Basic Clini. Med. 2014, 34, 654–660.
[50]	Li, B. M.S. thesis, Fourth Military Medical University. 2014.
[51]	Rastrelli, M.; Tropea, S.; Rossi, C.R.; Alaibac, M. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. Vivo. 2014, 28, 1005–1011.
[52]	Wu, M.L.; Luo, Y.Y.; Yan, X.; Chen, L.Y.; Cui, Y.R.; Liu, P.; Xie, X.X.; Yu, J. Preliminary study on the effect and Mechanism of Pulsatilla officinalis saponins on inflammatory factors in B16-F10 melanoma-bearing mice. Chin. Tradit. Patent Med. 2020, 42, 1609–1614.

白头翁皂苷及其单体抗肿瘤作用及机制的研究进展

Advances in anti-tumor effects and mechanisms of Pulsatilla Chinensis saponins and its monomers

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