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. 2022 Jun 16;27(12):3865.
doi: 10.3390/molecules27123865.

Acridone Derivatives from Atalantia monophyla Inhibited Cancer Cell Proliferation through ERK Pathway

Affiliations

Acridone Derivatives from Atalantia monophyla Inhibited Cancer Cell Proliferation through ERK Pathway

Wen-Yong Gao et al. Molecules. .

Abstract

The present study aimed to investigate the effect of acridone alkaloids on cancer cell lines and elucidate the underlying molecular mechanisms. The ten acridone alkaloids from Atalantia monophyla were screened for cytotoxicity against LNCaP cell lines by a WST-8 assay. Then, the most potential acridone, buxifoliadine E, was evaluated on four types of cancer cells, namely prostate cancer (LNCaP), neuroblastoma (SH SY5Y), hepatoblastoma (HepG2), and colorectal cancer (HT29). The results showed that buxifoliadine E was able to significantly inhibit the proliferation of all four types of cancer cells, having the most potent cytotoxicity against the HepG2 cell line. Western blotting analysis was performed to assess the expression of signaling proteins in the cancer cells. In HepG2 cells, buxifoliadine E induced changes in the levels of Bid as well as cleaved caspase-3 and Bax through MAPKs, including Erk and p38. Moreover, the binding interaction between buxifoliadine E and Erk was investigated by using the Autodock 4.2.6 and Discovery Studio programs. The result showed that buxifoliadine E bound at the ATP-binding site, located at the interface between the N- and C-terminal lobes of Erk2. The results of this study indicate that buxifoliadine E suppressed cancer cell proliferation by inhibiting the Erk pathway.

Keywords: Akt; Erk; apoptosis; buxifoliadine E; cancer cells; p38.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of acridone alkaloids.
Figure 1
Figure 1
Structures of acridone alkaloids.
Figure 2
Figure 2
The cytotoxicity effect of acridone alkaloids N-methylatalaphylline (A1), atalaphylline (A2), N-methylatalaphyllinine (A3), atalaphyllinine (A4), N-methylcycloatalaphylline A (A5), citrusinine II (A6), citrusinine I (A7), glycosparvarine (A8), citruscridone (A9), and buxifoliadine E (A10)) on LNCaP cell line. Data are the means ± SD of at least three independent experiments; * p < 0.05, ** p < 0.01 by One-way ANOVA.
Figure 3
Figure 3
Dose-response and time-course experiment. LNCaP cells were treated with various concentrations of buxifoliadine E for 24 h, 48 h, and 72 h. * p < 0.05.
Figure 4
Figure 4
Effect of buxifoliadine E on LNCaP cancer cell death. * p < 0.05.
Figure 5
Figure 5
Effect of buxifoliadine E on HepG2 cancer cell death. ** p < 0.01.
Figure 6
Figure 6
Effect of buxifoliadine E on HT29 cancer cell death. * p < 0.05.
Figure 7
Figure 7
Effect of buxifoliadine E on SHSY5Y cancer cell death. * p < 0.05.
Figure 8
Figure 8
Buxifoliadine E induces apoptosis of HepG2 cells.
Figure 9
Figure 9
Buxifoliadine E induces apoptosis of HepG2 cells through the Erk pathway.
Figure 10
Figure 10
Effect of buxifoliadine E on Erk enzyme-kinase activity. * p < 0.05, ** p < 0.01.
Figure 11
Figure 11
Binding modes and binding-interaction diagrams of buxifoliadine E bound to Erk. (A): buxifoliadine E bound at the ATP-binding site of Erk; (B): binding interaction between buxifoliadine E and Erk; (C): binding-interaction diagrams of buxifoliadine E and Erk.
Figure 12
Figure 12
Binding modes and binding-interaction diagrams of Erk inhibitor PD98059, PD bound to Erk. (A): PD bound at the ATP-binding site of Erk; (B): binding interaction between PD and Erk; (C): binding-interaction diagrams of PD and Erk.
Figure 13
Figure 13
Buxifoliadine E inhibits cell proliferation and induces apoptosis through Erk pathways.

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References

    1. 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;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Byung H.C., Shigeo H., Chiong E. The incidence, mortality, and risk factors of prostate cancer in Asian men. Prostate Int. 2019;7:1–8. - PMC - PubMed
    1. Gann P.H. Risk factors for prostate cancer. Rev. Urol. 2002;4:S3–S10. - PMC - PubMed
    1. Patel A.R., Klein E.A. Risk factors for prostate cancer. Nat. Clin. Pract. Urol. 2009;6:87–95. doi: 10.1038/ncpuro1290. - DOI - PubMed
    1. GBD 2015 Risk Factors Collaborators Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1659–1724. doi: 10.1016/S0140-6736(16)31679-8. - DOI - PMC - PubMed