Efficacy of Luteolin on the Human Gastric Cancer Cell Line MKN45 and Underlying Mechanism

Overview

Journal J Tradit Chin Med

Date 2023 Jan 14

PMID 36639993

Authors

Ding Yajie

Liu Feng

L I Zhaoyan

Xu Yan

Cao Nida

Zhang Guangao

Wang Rui

Zhao Aiguang

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the antitumour efficacy of luteolin on gastric cancer (GC) and study the mechanism underpinning the action.

Methods: Effects of luteolin on cell growth inhibition, apoptosis, and cell cycle arrest in MKN45 cells were investigated using the cell counting kit-8 assay. Changes in the mitochondrial membrane potential after luteolin treatment were assessed using 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanineiodi-de (JC-1) staining. To investigate whether apoptotic effect by luteolin is related to the phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) pathway, cells were additionally treated with LY294002, a PI3K/Akt pathway inhibitor. Moreover, the expressions of apoptosis-related proteins, namely B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein (Bax), Akt, p-Akt, caspase-3, and cytochrome C, were detected after luteolin treatment.

Results: The study revealed that in MKN45 cells, luteolin could inhibit the cell proliferation in a time- and dose-dependent manner; block the cell cycle in the S-phase; induce apoptosis; reduce the mitochondrial membrane potential; increase the expression of Bax, caspase-3, and cytochrome C; and decrease the expression of Bcl-2 and p-Akt. Luteolin might be involved in the PI3K/Akt signalling pathway, indicating that this pathway could be a therapeutic target for GC treatment.

Conclusion: Luteolin could inhibit the proliferation of GC cells and block the cell cycle in the S-phase. The mechanism of inducing apoptosis in these cells was related to the PI3K/Akt signalling pathway.

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References

Lu X, Li Y, Li X, Aisa H . Luteolin induces apoptosis through suppressing the MAPK and PI3K signaling pathways in gastric cancer. Oncol Lett. 2017; 14(2):1993-2000. PMC: 5530081. DOI: 10.3892/ol.2017.6380. View

Liu Q, Dong H, Sun W, Liu M, Ibla J, Liu L . Apoptosis initiation of β-ionone in SGC-7901 gastric carcinoma cancer cells via a PI3K-AKT pathway. Arch Toxicol. 2012; 87(3):481-90. DOI: 10.1007/s00204-012-0962-8. View

Tan J, Tian Y, Cai R, Yi T, Jin D, Guo J . Antiproliferative and Proapoptotic Effects of a Protein Component Purified from Dallas on Cancer Cells and . Evid Based Complement Alternat Med. 2019; 2019:8934794. PMC: 6335791. DOI: 10.1155/2019/8934794. View

Huang L, Jin K, Lan H . Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase. Oncol Lett. 2019; 17(4):3842-3850. PMC: 6425390. DOI: 10.3892/ol.2019.10052. View

Faes S, Dormond O . PI3K and AKT: Unfaithful Partners in Cancer. Int J Mol Sci. 2015; 16(9):21138-52. PMC: 4613246. DOI: 10.3390/ijms160921138. View

Chen K, Hsu W, Ho J, Lin C, Chu C, Kandaswami C . Flavonoids Luteolin and Quercetin Inhibit RPS19 and contributes to metastasis of cancer cells through c-Myc reduction. J Food Drug Anal. 2018; 26(3):1180-1191. PMC: 9303038. DOI: 10.1016/j.jfda.2018.01.012. View

Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N . Apoptosis and molecular targeting therapy in cancer. Biomed Res Int. 2014; 2014:150845. PMC: 4075070. DOI: 10.1155/2014/150845. View

Allemani C, Weir H, Carreira H, Harewood R, Spika D, Wang X . Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2014; 385(9972):977-1010. PMC: 4588097. DOI: 10.1016/S0140-6736(14)62038-9. View

Dai Z, Gao J, Ji Z, Wang X, Ren H, Liu X . Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. J Ethnopharmacol. 2009; 123(1):91-6. DOI: 10.1016/j.jep.2009.02.022. View

10.

Du L, Fei Z, Song S, Wei N . Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. Biomed Pharmacother. 2017; 95:447-452. DOI: 10.1016/j.biopha.2017.08.119. View

11.

Hasibuan P, Harahap U, Sitorus P, Satria D . The anticancer activities of Delile. Leaves on 4T1 breast cancer cells through phosphoinositide 3-kinase (PI3K) pathway. Heliyon. 2020; 6(7):e04449. PMC: 7371756. DOI: 10.1016/j.heliyon.2020.e04449. View

12.

Hoxhaj G, Manning B . The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 2019; 20(2):74-88. PMC: 7314312. DOI: 10.1038/s41568-019-0216-7. View

13.

Yan W, Ma X, Zhao X, Zhang S . Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro. Drug Des Devel Ther. 2018; 12:3961-3972. PMC: 6248272. DOI: 10.2147/DDDT.S181939. View

14.

Sathe A, Nawroth R . Targeting the PI3K/AKT/mTOR Pathway in Bladder Cancer. Methods Mol Biol. 2017; 1655:335-350. DOI: 10.1007/978-1-4939-7234-0_23. View

15.

Kou Y, Tong B, Wu W, Liao X, Zhao M . Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer. Front Pharmacol. 2020; 11:616251. PMC: 7756080. DOI: 10.3389/fphar.2020.616251. View

16.

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

17.

Davern M, Lysaght J . Cooperation between chemotherapy and immunotherapy in gastroesophageal cancers. Cancer Lett. 2020; 495:89-99. DOI: 10.1016/j.canlet.2020.09.014. View

18.

Valastyan S, Weinberg R . Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011; 147(2):275-92. PMC: 3261217. DOI: 10.1016/j.cell.2011.09.024. View

19.

Yin J, Ji Z, Hong Y, Song Z, Hu N, Zhuang M . Sh-MARCH8 Inhibits Tumorigenesis via PI3K Pathway in Gastric Cancer. Cell Physiol Biochem. 2018; 49(1):306-321. DOI: 10.1159/000492882. View

20.

Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati M, Ali Khan I . Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019; 112:108612. DOI: 10.1016/j.biopha.2019.108612. View