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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Pulsatilla saponin A Induces Apoptosis and Differentiation of Myeloma Cells

Author(s): Bibo Ye, Yingying Zhou, Yanli Liu, Xuewei Li, Tianyu Li* and Xiaofei Qi*

Volume 21, Issue 7, 2021

Published on: 21 July, 2020

Page: [919 - 926] Pages: 8

DOI: 10.2174/1871520620666200721125036

Price: $65

Abstract

Objectives: To investigate the performance of Pulsatilla saponin A (PsA) in Multiple Myeloma (MM) cells.

Methods: Proliferation, cell cycle analysis, apoptosis and TUNEL assays were conducted to detect the growth and apoptosis in MM cells. Western blotting was used to identify the change in the protein.

Results: In cell assays, PsA significantly inhibited the growth and apoptosis in MM cells. Cyclin B1, caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, p-ERK increased, while Bcl-2 decreased after PSA treatment. The CD49e positive rate of U266 cells was increased after 96h PsA treatment. At the same time, immunoglobulin and the Free Light Chain (FLC) ratio in the culture supernatant obviously increased. Also, the differentiation induced by PsA was confirmed in the primary myeloma cells.

Conclusion: Our findings reveal that PsA may exert its antitumor effect by causing G2 arrest and apoptosis in myeloma cells. And low-dose PsA can induce the differentiation of myeloma cell lines and primary myeloma cells, probably through the MEK/ERK signaling pathway in vitro.

Keywords: Pulsatilla saponin A (PsA), myeloma, apoptosis, differentiation, ERK signaling pathway, MEK.

Graphical Abstract

[1]
Perrotta, C.; Staines, A.; Codd, M.; Kleefeld, S.; Crowley, D.T.; Mannetje, A.; Becker, N.; Brennan, P.; De Sanjose, S.; Foretova, L.; Maynadie, M.; Nieters, A.; Boffetta, P.; Cocco, P. Multiple myeloma and lifetime occupation: Results from the EPILYMPH study. J. Occup. Med. Toxicol., 2012, 7(1), 25.
[http://dx.doi.org/10.1186/1745-6673-7-25] [PMID: 23241100]
[2]
Brown, R.E.; Stern, S.; Dhanasiri, S.; Schey, S. Lenalidomide for multiple myeloma: Cost-effectiveness in patients with one prior therapy in England and Wales. Eur. J. Health Econ., 2013, 14(3), 507-514.
[http://dx.doi.org/10.1007/s10198-012-0395-6] [PMID: 22572968]
[3]
Cheng, L.; Zhang, M.; Zhang, P.; Song, Z.; Ma, Z.; Qu, H. Silver complexation and tandem mass spectrometry for differentiation of triterpenoid saponins from the roots of Pulsatilla chinensis (Bunge). Regel. Rapid Commun. Mass Spectrom., 2008, 22(23), 3783-3790.
[http://dx.doi.org/10.1002/rcm.3801] [PMID: 18973198]
[4]
Xu, Q.M.; Shu, Z.; He, W.J.; Chen, L.Y.; Yang, S.L.; Yang, G.; Liu, Y.L.; Li, X.R. Antitumor activity of Pulsatilla chinensis (Bunge) Regel saponins in human liver tumor 7402 cells in vitro and in vivo. Phytomedicine, 2012, 19(3-4), 293-300.
[http://dx.doi.org/10.1016/j.phymed.2011.08.066] [PMID: 22001699]
[5]
Shi, B.J.; Li, Q.; Zhang, X.Q.; Wang, Y.; Ye, W.C.; Yao, X.S. Triterpene glycosides from the aerial parts of Pulsatilla chinensis. Yao Xue Xue Bao, 2007, 42(8), 862-866.
[PMID: 17944236]
[6]
Kim, Y.; Bang, S.C.; Lee, J.H.; Ahn, B.Z. Pulsatilla saponin D: The antitumor principle from Pulsatilla koreana. Arch. Pharm. Res., 2004, 27(9), 915-918.
[http://dx.doi.org/10.1007/BF02975843] [PMID: 15473660]
[7]
Tin, M.M.; Cho, C.H.; Chan, K.; James, A.E.; Ko, J.K. Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis, 2007, 28(6), 1347-1355.
[http://dx.doi.org/10.1093/carcin/bgl238] [PMID: 17148504]
[8]
Liu, Q.; Chen, W.; Jiao, Y.; Hou, J.; Wu, Q.; Liu, Y.; Qi, X. 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(2), 387-395.
[http://dx.doi.org/10.1016/j.jss.2014.01.026] [PMID: 24576780]
[9]
Wang, T.; Gong, F.; Zhang, R.; Cen, J.; Dai, L.; Zhu, M.; Qi, X. Pulsatilla saponin A induces differentiation in acute myeloid leukemia in vitro. Hematology, 2016, 21(3), 182-186.
[http://dx.doi.org/10.1080/10245332.2015.1101967] [PMID: 26868262]
[10]
Son, M.K.; Jung, K.H.; Hong, S.W.; Lee, H.S.; Zheng, H.M.; Choi, M.J.; Seo, J.H.; Suh, J.K.; Hong, S.S. SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway. Food Chem., 2013, 136(1), 26-33.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.096] [PMID: 23017388]
[11]
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. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2016, 24(4), 975-979.
[PMID: 27531759]
[12]
Van Riet, I.; Van Camp, B. The involvement of adhesion molecules in the biology of multiple myeloma. Leuk. Lymphoma, 1993, 9(6), 441-452.
[http://dx.doi.org/10.3109/10428199309145751] [PMID: 8339050]
[13]
Chillemi, A.; Zaccarello, G.; Quarona, V.; Lazzaretti, M.; Martella, E.; Giuliani, N.; Ferracini, R.; Pistoia, V.; Horenstein, A.L.; Malavasi, F. CD38 and bone marrow microenvironment. Front. Biosci., 2014, 19, 152-162.
[http://dx.doi.org/10.2741/4201] [PMID: 24389178]
[14]
Sher, T.; Gertz, M.A. Antibody based immunotherapy for multiple myeloma: It’s about time. Leuk. Lymphoma, 2015, 16(12), 1-7.
[PMID: 26373636]
[15]
de Weers, M.; Tai, Y.T.; van der Veer, M.S.; Bakker, J.M.; Vink, T.; Jacobs, D.C.; Oomen, L.A.; Peipp, M.; Valerius, T.; Slootstra, J.W.; Mutis, T.; Bleeker, W.K.; Anderson, K.C.; Lokhorst, H.M.; van de Winkel, J.G.; Parren, P.W. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J. Immunol., 2011, 186(3), 1840-1848.
[http://dx.doi.org/10.4049/jimmunol.1003032] [PMID: 21187443]
[16]
van de Donk, N.W.; Janmaat, M.L.; Mutis, T.; Lammerts van Bueren, J.J.; Ahmadi, T.; Sasser, A.K.; Lokhorst, H.M.; Parren, P.W. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol. Rev., 2016, 270(1), 95-112.
[http://dx.doi.org/10.1111/imr.12389] [PMID: 26864107]
[17]
Greipp, P.R.; Raymond, N.M.; Kyle, R.A.; O’Fallon, W.M. Multiple myeloma: Significance of plasmablastic subtype in morphological classification. Blood, 1985, 65(2), 305-310.
[http://dx.doi.org/10.1182/blood.V65.2.305.305] [PMID: 3967084]
[18]
Kawano, M.M.; Huang, N.; Harada, H.; Harada, Y.; Sakai, A.; Tanaka, H.; Iwato, K.; Kuramoto, A. Identification of immature and mature myeloma cells in the bone marrow of human myelomas. Blood, 1993, 82(2), 564-570.
[http://dx.doi.org/10.1182/blood.V82.2.564.564] [PMID: 8329711]
[19]
Wang, P.F.; Xu, Y.; Yan, S.; Yao, Y.; Zheng, H.F.; Ma, L.; Jin, S.; Xu, Y.; Gong, F.R.; Zhou, J.Z.; Chang, H.R.; Fu, C.C. The roles of serum free light chain ratio in the diagnosis and prognosis of newly diagnosed multiple myeloma. Zhonghua Xue Ye Xue Za Zhi, 2016, 37(5), 377-382.
[PMID: 27210871]
[20]
Dispenzieri, A.; Kyle, R.A.; Katzmann, J.A.; Therneau, T.M.; Larson, D.; Benson, J.; Clark, R.J.; Melton, L.J., III; Gertz, M.A.; Kumar, S.K.; Fonseca, R.; Jelinek, D.F.; Rajkumar, S.V. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood, 2008, 111(2), 785-789.
[http://dx.doi.org/10.1182/blood-2007-08-108357] [PMID: 17942755]
[21]
Dingli, D.; Kyle, R.A.; Rajkumar, S.V.; Nowakowski, G.S.; Larson, D.R.; Bida, J.P.; Gertz, M.A.; Therneau, T.M.; Melton, L.J., III; Dispenzieri, A.; Katzmann, J.A. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood, 2006, 108(6), 1979-1983.
[http://dx.doi.org/10.1182/blood-2006-04-015784] [PMID: 16741249]
[22]
Rajkumar, S.V.; Kyle, R.A.; Therneau, T.M.; Melton, L.J., III; Bradwell, A.R.; Clark, R.J.; Larson, D.R.; Plevak, M.F.; Dispenzieri, A.; Katzmann, J.A. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood, 2005, 106(3), 812-817.
[http://dx.doi.org/10.1182/blood-2005-03-1038] [PMID: 15855274]
[23]
Iwama, K.; Chihara, D.; Tsuda, K.; Ugai, T.; Sugihara, H.; Nishida, Y.; Yamakura, M.; Takeuchi, M.; Matsue, K. Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma. Eur. J. Haematol., 2013, 90(2), 134-141.
[http://dx.doi.org/10.1111/ejh.12050] [PMID: 23210517]
[24]
Yağcı, M.; Karakaya, F.; Suyanı, E.; Haznedar, R. Serum free light chain response after 2 courses of induction chemotherapy predicts prognosis in myeloma patients. Clin. Lymphoma Myeloma Leuk., 2015, 15(2), 98-102.
[http://dx.doi.org/10.1016/j.clml.2014.08.007] [PMID: 25441109]

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