Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Gambogic Acid Lysinate-induced Cervical Cancer SiHa Cells Apoptosis in vitro and in vivo

Author(s): Jie Niu, Jingyu Sun, Yahua Liu, Jun Guo, Xin Zhang and Yajun Lin*

Volume 23, Issue 11, 2023

Published on: 16 March, 2023

Page: [1320 - 1326] Pages: 7

DOI: 10.2174/1871520623666230223145706

Price: $65

conference banner
Abstract

Background: Surgical resection and chemotherapy are the primary treatment options for cervical cancer; however, efficacy of chemotherapy drugs is limited by drug resistance. There is an urgent need to find new compounds. Gambogic acid lysinate (GAL), a new compound made from gambogic acid and lysine, has good anti-tumor activity, however, the effect of GAL on cervical cancer remains undetermined.

Objective: The present study sought to explore the anti-tumor activity of GAL in SiHa cells.

Methods: Cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, and Western blotting was employed to explore the mechanism of GAL. Additionally, the in vivo anti-tumor activity of GAL was studied through a xenograft tumor model in nude mice.

Results: GAL inhibited the proliferation of both SiHa cells (IC50 was 0.83 μmol/l and 0.77 μmol/l respectively for 48 h and 72 h) and HeLa cells (IC50 did not reach). In SiHa cells, GAL (1 and 2 μmol/l) inhibited cell proliferation and 2 μmol/l GAL could also induce cell apoptosis and decrease the number of S phase. Both 1 and 2 μmol/l GAL inhibited SiHa cells invasion and increased the number of G0/G1 phase. The results of Western blot assay demonstrated that P53 and P21 were involved in SiHa cells S phase arrest and BCL-2 and BAX were involved in SiHa cells apoptosis. In vivo study showed that the growth of SiHa cell xenograft tumors was inhibited via cell apoptosis induced by GAL (2.5 mg/kg body weight), however, GAL (2.5 mg/kg body weight) had no significant effect on weight gain of mice.

Conclusion: GAL induced SiHa cells apoptosis by BCL-2 and BAX pathway and SiHa cells S phase arrest by P53 and P21 pathway in vitro and inhibited the growth of SiHa cell xenograft tumors.

« Previous Next »
Graphical Abstract

[1]
Olusola, P.; Banerjee, H.N.; Philley, J.V.; Dasgupta, S. Human papilloma virus-associated cervical cancer and health disparities. Cells, 2019, 8(6), 622.
[http://dx.doi.org/10.3390/cells8060622] [PMID: 31234354]
[2]
Cohen, P.A.; Jhingran, A.; Oaknin, A.; Denny, L. Cervical cancer. Lancet, 2019, 393(10167), 169-182.
[http://dx.doi.org/10.1016/S0140-6736(18)32470-X] [PMID: 30638582]
[3]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[4]
Di, J.; Rutherford, S.; Chu, C. Review of the cervical cancer burden and population-based cervical cancer screening in China. Asian Pac. J. Cancer Prev., 2015, 16(17), 7401-7407.
[http://dx.doi.org/10.7314/APJCP.2015.16.17.7401] [PMID: 26625735]
[5]
Hull, R.; Mbele, M.; Makhafola, T.; Hicks, C.; Wang, S.M.; Reis, R.; Mehrotra, R.; Mkhize-Kwitshana, Z.; Kibiki, G.; Bates, D.; Dlamini, Z. Cervical cancer in low and middle income countries. Oncol. Lett., 2020, 20(3), 2058-2074.
[http://dx.doi.org/10.3892/ol.2020.11754] [PMID: 32782524]
[6]
Wang, X.; Chen, W. Gambogic acid is a novel anti-cancer agent that inhibits cell proliferation, angiogenesis and metastasis. Anticancer. Agents Med. Chem., 2012, 12(8), 994-1000.
[http://dx.doi.org/10.2174/187152012802650066] [PMID: 22339063]
[7]
Wang, W.; Li, Y.; Chen, Y.; Chen, H.; Zhu, P.; Xu, M.; Wang, H.; Wu, M.; Yang, Z.; Hoffman, R.M.; Gu, Y. Ethanolic extract of traditional chinese medicine (TCM) Gamboge inhibits colon cancer via the wnt/beta-catenin signaling pathway in an orthotopic mouse model. Anticancer Res., 2018, 38(4), 1917-1925.
[http://dx.doi.org/10.21873/anticanres.12429] [PMID: 29599307]
[8]
Li, M.; Su, F.L.; Zhu, M.T.; Zhang, H.; Wei, Y.X.; Zhao, Y.; Li, J.M.; Lv, S.W. Research progress in the field of gambogic acid and its derivatives as antineoplastic drugs. Molecules, 2022, 27(9), 2937.
[http://dx.doi.org/10.3390/molecules27092937]
[9]
Wang, Y.; Sui, Y.; Tao, Y. Gambogic acid increases the sensitivity to paclitaxel in drug resistant triple negative breast cancer via the SHH signaling pathway. Mol. Med. Rep., 2019, 20(5), 4515-4522.
[http://dx.doi.org/10.3892/mmr.2019.10697] [PMID: 31545492]
[10]
Zhao, T.; Wang, H.J.; Zhao, W.W.; Sun, Y.L.; Hu, L.K. Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway. Kaohsiung J. Med. Sci., 2017, 33(11), 543-549.
[http://dx.doi.org/10.1016/j.kjms.2017.06.013] [PMID: 29050671]
[11]
Zhen, Y.Z.; Lin, Y.J.; Li, K.J.; Yang, X.S.; Zhao, Y.F.; Wei, J.; Wei, J.B.; Hu, G. Gambogic acid lysinate induces apoptosis in breast cancer MCF-7 cells by increasing reactive oxygen species. Evid. Based Compl. Altern. Med., 2015, 2015842091
[http://dx.doi.org/10.1155/2015/842091] [PMID: 25866542]
[12]
Jones, J.I.; Gockerman, A.; Busby, W.H., Jr; Wright, G.; Clemmons, D.R. Insulin-like growth factor binding protein 1 stimulates cell mi-gration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. Proc. Natl. Acad. Sci. USA, 1993, 90(22), 10553-10557.
[http://dx.doi.org/10.1073/pnas.90.22.10553] [PMID: 7504269]
[13]
Hu, Y.; Rao, S.S.; Wang, Z.X.; Cao, J.; Tan, Y.J.; Luo, J.; Li, H.M.; Zhang, W.S.; Chen, C.Y.; Xie, H. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function. Theranostics, 2018, 8(1), 169-184.
[http://dx.doi.org/10.7150/thno.21234] [PMID: 29290800]
[14]
Cao, W.; Chen, H.D.; Yu, Y.W.; Li, N.; Chen, W.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J., 2021, 134(7), 783-791.
[http://dx.doi.org/10.1097/CM9.0000000000001474] [PMID: 33734139]
[15]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[16]
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(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[17]
Lin, J.; Chen, L.; Qiu, X.; Zhang, N.; Guo, Q.; Wang, Y.; Wang, M.; Gober, H.J.; Li, D.; Wang, L. Traditional Chinese medicine for human papillomavirus (HPV) infections: A systematic review. Biosci. Trends, 2017, 11(3), 267-273.
[http://dx.doi.org/10.5582/bst.2017.01056] [PMID: 28484110]
[18]
Banik, K.; Harsha, C.; Bordoloi, D.; Lalduhsaki Sailo, B.; Sethi, G.; Leong, H.C.; Arfuso, F.; Mishra, S.; Wang, L.; Kumar, A.P.; Kun-numakkara, A.B. Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Lett., 2018, 416, 75-86.
[http://dx.doi.org/10.1016/j.canlet.2017.12.014] [PMID: 29246645]
[19]
Reszegi, A.; Horváth, Z.; Karászi, K.; Regős, E.; Postniková, V.; Tátrai, P.; Kiss, A.; Schaff, Z.; Kovalszky, I.; Baghy, K. The protective role of decorin in hepatic metastasis of colorectal carcinoma. Biomolecules, 2020, 10(8), 1199.
[http://dx.doi.org/10.3390/biom10081199] [PMID: 32824864]
[20]
Frame, F.M.; Rogoff, H.A.; Pickering, M.T.; Cress, W.D.; Kowalik, T.F. E2F1 induces MRN foci formation and a cell cycle checkpoint response in human fibroblasts. Oncogene, 2006, 25(23), 3258-3266.
[http://dx.doi.org/10.1038/sj.onc.1209352] [PMID: 16434972]
[21]
Shamsi-Gamchi, N.; Razi, M.; Behfar, M. Cross-link between mitochondrial-dependent apoptosis and cell cycle checkpoint proteins after experimental torsion and detorsion in rats. Gene, 2021, 795145793
[http://dx.doi.org/10.1016/j.gene.2021.145793] [PMID: 34175398]
[22]
Desroches, A.; Denault, J.B. Characterization of caspase-7 interaction with RNA. Biochem. J., 2021, 478(13), 2681-2696.
[http://dx.doi.org/10.1042/BCJ20210366] [PMID: 34156061]
[23]
Choi, H.S.; Han, S.; Yokota, H.; Cho, K.H. Coupled positive feedbacks provoke slow induction plus fast switching in apoptosis. FEBS Lett., 2007, 581(14), 2684-2690.
[http://dx.doi.org/10.1016/j.febslet.2007.05.016] [PMID: 17532319]
[24]
Xiao, Z-J.; Wu, H.; Tan, J.; Chen, S-X.; Lei, Q-Y.; Yi, S-Q.; Wu, N.; Wang, Y-L. Mitochonic acid 5 regulates mitofusin 2 to protect micro-glia. Neural Regen. Res., 2021, 16(9), 1813-1820.
[http://dx.doi.org/10.4103/1673-5374.306094] [PMID: 33510088]
[25]
Bas, J.; Nguyen, T.; Gillet, G. Involvement of Bcl-xL in neuronal function and development. Int. J. Mol. Sci., 2021, 22(6), 3202.
[http://dx.doi.org/10.3390/ijms22063202] [PMID: 33801158]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy