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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Buddleoside Inhibits Progression of Liver Cancer by Regulating NFκB Signaling Pathway

Author(s): Li Zhang, Lizhi Sun, Shuchun Gao, Weihua Yang, Yuanmei Zhuang and Mingjie Xu*

Volume 21, Issue 1, 2024

Published on: 04 April, 2023

Page: [166 - 173] Pages: 8

DOI: 10.2174/1570180820666230308115303

Price: $65

Abstract

Background: Liver cancer is a severe incurable disease and causes several thousands of deaths each year. Flavonoids are a class of bioactive compounds possessing anti-cancer activity.

Objective: The objective of this study is to investigate the role of Buddleoside, one type of flavonoids, in carcinogenesis of liver cancer.

Methods: Cell proliferation was detected by CCK-8 method, while cell invasion was by transwell assay, cell apoptosis by Annexin V/FITC-A staining. Western blotting technology was used to explore the mechanism of Buddleoside in liver cancer.

Results: It was demonstrated that buddleoside inhibited cell proliferation in a dose-dependent manner and suppressed cell invasion in liver cancer. The inhibition rates of buddleoside in the invasion of both Huh-7 and Hep3B cells were above 75%. The apoptotic rates in the two cell lines were increased by about 10 folds in buddleoside group. Then, the expression levels of NFκB/p65 and IKK were decreased when IκB increased in buddleoside-treated Huh-7 cells, suggesting the inhibition of NFκB signaling pathway. Moreover, the expression levels of cleaved caspase-3 and Bax were upregulated while HSDL2 decreased in buddleoside group. In contrast, after NFκB/p65 was overexpressed, the expression patterns of these molecules were reversed partially. Consistently, the abilities of cell proliferation and cell invasion were recovered, while cell apoptosis decreased after NFκB/p65 overexpression.

Conclusion: Buddleoside inhibits proliferation, and invasion and induces apoptosis in liver cancer by regulating NFκB signaling pathway. This study provides us with new proofs for the possible application of buddleoside in liver cancer therapy.

Keywords: Buddleoside, liver cancer, NFκB signaling pathway, Caspase-3, bioactive compounds, CCK-8 method, TCM.

Graphical Abstract
[1]
Anwanwan, D.; Singh, S.K.; Singh, S.; Saikam, V.; Singh, R. Challenges in liver cancer and possible treatment approaches. Biochim. Biophys. Acta Rev. Cancer, 2020, 1873(1), 188314.
[http://dx.doi.org/10.1016/j.bbcan.2019.188314] [PMID: 31682895]
[2]
Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin., 2023, 73(1), 17-48.
[http://dx.doi.org/10.3322/caac.21763] [PMID: 36633525]
[3]
Maki, H.; Hasegawa, K. Advances in the surgical treatment of liver cancer. Biosci. Trends, 2022, 16(3), 178-188.
[http://dx.doi.org/10.5582/bst.2022.01245] [PMID: 35732434]
[4]
Tian, B.; Li, Q. Single-cell sequencing and its application in liver cancer. Front. Oncol., 2022, 12, 857037.
[http://dx.doi.org/10.3389/fonc.2022.857037] [PMID: 35574365]
[5]
Musyuni, P.; Bai, J.; Sheikh, A.; Vasanthan, K.S.; Jain, G.K.; Abourehab, M.A.S.; Lather, V.; Aggarwal, G.; Kesharwani, P.; Pandita, D. Precision medicine: Ray of hope in overcoming cancer multidrug resistance. Drug Resist. Updat., 2022, 65, 100889.
[http://dx.doi.org/10.1016/j.drup.2022.100889] [PMID: 36403342]
[6]
Wang, Y.J.; Su, J.; Yu, J.J.; Yan, M.Q.; Shi, M.L.; Huang, Q.D.; Li, B.; Wu, W.Y.; Xia, R.S.; Li, S.F.; Chen, S.H.; Lv, G.Y. Buddleoside-Rich Chrysanthemum indicum L. extract has a beneficial effect on metabolic hypertensive rats by inhibiting the enteric-origin LPS/TLR4 pathway. Front. Pharmacol., 2021, 12, 755140.
[http://dx.doi.org/10.3389/fphar.2021.755140] [PMID: 34690786]
[7]
Wang, Z.; Lv, J.; Li, X.; Lin, Q. The flavonoid astragalin shows anti‐tumor activity and inhibits PI3K/AKT signaling in gastric cancer. Chem. Biol. Drug Des., 2021, 98(5), 779-786.
[http://dx.doi.org/10.1111/cbdd.13933] [PMID: 34396710]
[8]
Yang, Y.; Chen, B.; Liang, K.L.; Su, J.; Chen, S.H.; Lv, G.Y. Relaxation effect of buddleoside combined with luteolin on isolated vessels in vivo and its mechanism. Zhongguo Zhongyao Zazhi, 2017, 42(7), 1370-1375.
[PMID: 29052401]
[9]
Gai, Q.Y.; Jiao, J.; Luo, M.; Wei, Z.F.; Zu, Y.G.; Ma, W.; Fu, Y.J. Establishment of hairy root cultures by Agrobacterium rhizogenes mediated transformation of Isatis tinctoria L. For the efficient production of flavonoids and evaluation of antioxidant activities. PLoS One, 2015, 10(3), e0119022.
[http://dx.doi.org/10.1371/journal.pone.0119022] [PMID: 25785699]
[10]
Slika, H.; Mansour, H.; Wehbe, N.; Nasser, S.A.; Iratni, R.; Nasrallah, G.; Shaito, A.; Ghaddar, T.; Kobeissy, F.; Eid, A.H. Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed. Pharmacother., 2022, 146, 112442.
[http://dx.doi.org/10.1016/j.biopha.2021.112442] [PMID: 35062053]
[11]
Wen, K.; Fang, X.; Yang, J.; Yao, Y.; Nandakumar, K.S.; Salem, M.L.; Cheng, K. Recent research on flavonoids and their biomedical applications. Curr. Med. Chem., 2021, 28(5), 1042-1066.
[http://dx.doi.org/10.2174/1875533XMTA4BMTMl5] [PMID: 32660393]
[12]
Sui, X.; Han, X.; Chen, P.; Wu, Q.; Feng, J.; Duan, T.; Chen, X.; Pan, T.; Yan, L.; Jin, T.; Xiang, Y.; Gao, Q.; Wen, C.; Ma, W.; Liu, W.; Zhang, R.; Chen, B.; Zhang, M.; Yang, Z.; Kong, N.; Xie, T.; Ding, X. Baicalin induces apoptosis and suppresses the cell cycle progression of lung cancer cells through downregulating Akt/mTOR signaling pathway. Front. Mol. Biosci., 2021, 7, 602282.
[http://dx.doi.org/10.3389/fmolb.2020.602282] [PMID: 33585556]
[13]
Trybus, W.; Król, T.; Trybus, E.; Stachurska, A.; Król, G. The potential antitumor effect of chrysophanol in relation to cervical cancer cells. J. Cell. Biochem., 2021, 122(6), 639-652.
[http://dx.doi.org/10.1002/jcb.29891] [PMID: 33417255]
[14]
Hausman, D.M. What is cancer? Perspect. Biol. Med., 2019, 62(4), 778-784.
[http://dx.doi.org/10.1353/pbm.2019.0046] [PMID: 31761807]
[15]
Kaczanowski, S. Apoptosis: Its origin, history, maintenance and the medical implications for cancer and aging. Phys. Biol., 2016, 13(3), 031001.
[http://dx.doi.org/10.1088/1478-3975/13/3/031001] [PMID: 27172135]
[16]
Li, X.; He, S.; Ma, B. Autophagy and autophagy-related proteins in cancer. Mol. Cancer, 2020, 19(1), 12.
[http://dx.doi.org/10.1186/s12943-020-1138-4] [PMID: 31969156]
[17]
Liebl, M.C.; Hofmann, T.G. The role of p53 signaling in colorectal cancer. Cancers , 2021, 13(9), 2125.
[http://dx.doi.org/10.3390/cancers13092125] [PMID: 33924934]
[18]
Verzella, D.; Pescatore, A.; Capece, D.; Vecchiotti, D.; Ursini, M.V.; Franzoso, G.; Alesse, E.; Zazzeroni, F. Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis., 2020, 11(3), 210.
[http://dx.doi.org/10.1038/s41419-020-2399-y] [PMID: 32231206]
[19]
Willis, S.; Day, C.L.; Hinds, M.G.; Huang, D.C.S. The BCL-2-regulated apoptotic pathway. J. Cell Sci., 2003, 116(20), 4053-4056.
[http://dx.doi.org/10.1242/jcs.00754] [PMID: 12972498]
[20]
Dai, J.; Xie, Y.; Wu, Q.; Wang, L.; Yin, G.; Ye, X.; Zeng, L.; Xu, J.; Ji, C.; Gu, S.; Huang, Q.; Zhao, R.C.; Mao, Y. Molecular cloning and characterization of a novel human hydroxysteroid dehydrogenase-like 2 (HSDL2) cDNA from fetal brain. Biochem. Genet., 2003, 41(5/6), 165-174.
[http://dx.doi.org/10.1023/A:1023377627138] [PMID: 12834046]
[21]
Han, A.; Xu, R.; Liu, Y.; Yin, X.; Lin, Z.; Yang, W. HSDL2 acts as a promoter in pancreatic cancer by regulating cell proliferation and lipid metabolism. OncoTargets Ther., 2021, 14, 435-444.
[http://dx.doi.org/10.2147/OTT.S287722] [PMID: 33488098]
[22]
Yang, Y.; Han, A.; Wang, X.; Yin, X.; Cui, M.; Lin, Z. Lipid metabolism regulator human hydroxysteroid dehydrogenase‐like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis. J. Cell. Mol. Med., 2021, 25(10), 4846-4859.
[http://dx.doi.org/10.1111/jcmm.16461] [PMID: 33738911]

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