Terpene extract from the stem of <i>Celastrus orbiculatus</i> inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4

Zewen Chu; Miao Zhu; Yuanyuan Luo; Yaqi Hu; Xinyi Feng; Jiacheng Shen; Haibo Wang; Masataka Sunagawa; Yanqing Liu

doi:10.1016/j.jpha.2024.101021

Volume 14 Issue 8

Aug. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(8): 101021

Zewen Chu, Miao Zhu, Yuanyuan Luo, Yaqi Hu, Xinyi Feng, Jiacheng Shen, Haibo Wang, Masataka Sunagawa, Yanqing Liu. Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 101021. doi: 10.1016/j.jpha.2024.101021

Citation:

Zewen Chu, Miao Zhu, Yuanyuan Luo, Yaqi Hu, Xinyi Feng, Jiacheng Shen, Haibo Wang, Masataka Sunagawa, Yanqing Liu. Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 101021. doi: 10.1016/j.jpha.2024.101021

Citation:

PDF( 7019 KB)

Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4

doi: 10.1016/j.jpha.2024.101021

Zewen Chu^a,b,
Miao Zhu^a,b,
Yuanyuan Luo^a,b,
Yaqi Hu^a,b,
Xinyi Feng^a,b,
Jiacheng Shen^a,b,
Haibo Wang^{a,b
,
,},
Masataka Sunagawa^{c
,
,},
Yanqing Liu^{a,b
,
,}

a. Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, China;
b. The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, Jiangsu, 225001, China;
c. Department of Physiology, School of Medicine, Showa University, Tokyo, 142-8555, Japan

Funds:

Thanks for the Graphical abstract drawn by using Figdraw. We thank Wuhan Genecreate Biological Engineering Co., Ltd., China for the assistance with the Co-IP-MS analysis. We would like to express our gratitude to Shanghai Outdo Biotech Co., Ltd., China for supplying the tissue microarray of patients with GC and technical assistance for multiple IF. We also extend our gratitude to GemPharmatech Co., Ltd., China for the assistance in developing the PTBP1 Cas9-KO mouse model.

Received Date: Mar. 02, 2024
Accepted Date: Jun. 11, 2024
Rev Recd Date: Jun. 02, 2024
Publish Date: Jun. 13, 2024

Abstract

Abstract

Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.
- Traditional Chinese medicine,
- Polypyrimidine tract binding protein 1,
- Alpha actinin-4,
- Gastric cancer,
- Actin skeleton remodelling

FullText(HTML)

References(49)

References

[1]	E.C. Smyth, M. Nilsson, H.I. Grabsch, et al., Gastric cancer, Lancet. 396(2020) 635-648.
[2]	L. Seeneevassen, E. Bessede, F. Megraud, et al., Gastric cancer: advances in carcinogenesis research and new therapeutic strategies, Int. J. Mol. Sci. 22(2021), 3418.
[3]	Y. Lin, R. Shi, X. Wang, et al., Luteolin, a flavonoid with potential for cancer prevention and therapy, Curr. Cancer Drug Targets 8(2008) 634-646.
[4]	L. Ziberna, D. Samec, A. Mocan, et al., Oleanolic acid alters multiple cell signaling pathways: implication in cancer prevention and therapy, Int. J. Mol. Sci. 18(2017), 643.
[5]	S.-T. Wang, W.-Q. Cui, D. Pan, et al., Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer, World J. Gastroenterol. 26(2020) 562-597.
[6]	C.H. Ooi, T. Ivanova, J. Wu, et al., Oncogenic pathway combinations predict clinical prognosis in gastric cancer, PLoS Genet. 5(2009), e1000676.
[7]	O. Moujaber, U. Stochaj, The cytoskeleton as regulator of cell signaling pathways, Trends Biochem. Sci. 45(2020) 96-107.
[8]	W. Jung, A.P. Tabatabai, J.J. Thomas, et al., Dynamic motions of molecular motors in the actin cytoskeleton, Cytoskeleton 76(2019) 517-531.
[9]	S. Azadi, M. Tafazzoli-Shadpour, M. Soleimani, et al., Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations, J. Biomed. Mater. Res., Part A 107(2019) 1569-1581.
[10]	J.-M. Peng, R. Bera, C.-Y. Chiou, et al., Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice, Hepatology 67(2018) 2226-2243.
[11]	Y. Du, B. Jiang, S. Song, et al., Metadherin regulates actin cytoskeletal remodeling and enhances human gastric cancer metastasis via epithelial-mesenchymal transition, Int. J. Oncol. 51(2017) 63-74.
[12]	J. Zhang, Y. Zhou, P.M.K. Tang, et al., Mechanotransduction and cytoskeleton remodeling shaping YAP1 in gastric tumorigenesis, Int. J. Mol. Sci. 20(2019), 1576.
[13]	B. Ristic, J. Kopel, S.A.A. Sherazi, et al., Emerging role of fascin-1 in the pathogenesis, diagnosis, and treatment of the gastrointestinal cancers, Cancers 13(2021), 2536.
[14]	Q. Liu, J. Tang, S. Chen, et al., Berberine for gastric cancer prevention and treatment: multi-step actions on the Correa's cascade underlie its therapeutic effects, Pharmacol. Res. 184(2022), 106440.
[15]	L. Peng, Y. Dong, H. Fan, et al., Traditional Chinese medicine regulating lymphangiogenesis: a literature review, Front. Pharmacol. 11(2020), 1259.
[16]	M. Xu, Q. Cui, W. Su, et al., High-content screening of active components of Traditional Chinese Medicine inhibiting TGF-β-induced cell EMT, Heliyon 8(2022), e10238.
[17]	J. Bai, W.C. Kwok, J.-P. Thiery, Traditional Chinese Medicine and regulatory roles on epithelial-mesenchymal transitions, Chin. Med. 14(2019), 34.
[18]	J. Hernandez-Valencia, E. Garcia-Villa, A. Arenas-Hernandez, et al., Induction of p53 phosphorylation at serine 20 by resveratrol is required to activate p53 target genes, restoring apoptosis in MCF-7 cells resistant to cisplatin, Nutrients 10(2018), 1148.
[19]	R. Zhang, H. Qiao, S. Chen, et al., Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS, Cancer Biol. Ther. 17(2016) 925-934.
[20]	Y. Liu, Inventors; Total terpene extract of Celastrus orbiculatus stem, its preparation method and application, China patent, ZL 200710025343.3, 8 February 2012.
[21]	H. Wang, H. Gu, J. Feng, et al., Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer, Oncol. Lett. 14(2017) 2926-2932.
[22]	H. Wang, Y. Luo, S. Ou, et al., Celastrus orbiculatus Thunb. extract inhibits EMT and metastasis of gastric cancer by regulating actin cytoskeleton remodeling, J. Ethnopharmacol. 301(2023), 115737.
[23]	T. Ni, Z. Chu, L. Tao, et al., PTBP1 drives c-Myc-dependent gastric cancer progression and stemness, Br. J. Cancer 128(2023) 1005-1018.
[24]	Z. Chu, M. Zhu, Y. Luo, et al., PTBP1 plays an important role in the development of gastric cancer, Cancer Cell Int. 23(2023), 195.
[25]	T. Ni, Z. Chu, L. Tao, et al., Celastrus orbiculatus extract suppresses gastric cancer stem cells through the TGF-β/Smad signaling pathway, J. Nat. Med. 78(2024) 100-113.
[26]	W. Jiang, T.-Z. Shan, J.-J. Xu, et al., Cytotoxic abietane and kaurane diterpenoids from Celastrus orbiculatus, J. Nat. Med. 73(2019) 841-846.
[27]	Z. Chu, H. Wang, T. Ni, et al., 28-Hydroxy-3-oxoolean-12-en-29-oic acid, a triterpene acid from Celastrus orbiculatus extract, inhibits the migration and invasion of human gastric cancer cells in vitro, Molecules 24(2019), 3513.
[28]	Z. Tang, C. Li, B. Kang, et al., GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses, Nucleic Acids Res. 45(2017) W98-W102.
[29]	D. Feng, M. Kumar, J. Muntel, et al., Phosphorylation of ACTN4 leads to podocyte vulnerability and proteinuric glomerulosclerosis, J. Am. Soc. Nephrol. 31(2020) 1479-1495.
[30]	P.J. Simpson, T.P. Monie, A. Szendroi, et al., Structure and RNA interactions of the N-terminal RRM domains of PTB, Structure 12(2004) 1631-1643.
[31]	F. Vitali, A. Henning, F.C. Oberstrass, et al., Structure of the two most C-terminal RNA recognition motifs of PTB using segmental isotope labeling, EMBO J. 25(2006) 150-162.
[32]	F. Jin, X. Ni, S. Yu, et al., The Ethyl acetate extract from Celastrus orbiculatus suppresses non-small-cell lung cancer by activating Hippo signaling and inhibiting YAP nuclear translocation, Phytomedicine 114(2023), 154761.
[33]	O. Soderberg, M. Gullberg, M. Jarvius, et al., Direct observation of individual endogenous protein complexes in situ by proximity ligation, Nat. Methods 3(2006) 995-1000.
[34]	R. Moll, W.W. Franke, D.L. Schiller, et al., The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells, Cell 31(1982) 11-24.
[35]	C.A. Otey, O. Carpen, Alpha-actinin revisited: a fresh look at an old player, Cell Motil Cytoskeleton 58(2004) 104-111.
[36]	J.H. Brown, K.H. Kim, G. Jun, et al., Deciphering the design of the tropomyosin molecule, Proc. Natl. Acad. Sci. U. S. A. 98(2001) 8496-8501.
[37]	J.-D. Kai, L.-H. Cheng, B.-F. Li, et al., MYH9 is a novel cancer stem cell marker and prognostic indicator in esophageal cancer that promotes oncogenesis through the PI3K/AKT/mTOR axis, Cell Biol. Int. 46(2022) 2085-2094.
[38]	F. Rinaldi, C. Terracciano, V. Pisani, et al., Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues, Neurobiol. Dis. 45(2012) 264-271.
[39]	R. Athman, D. Louvard, S. Robine, The epithelial cell cytoskeleton and intracellular trafficking. III. How is villin involved in the actin cytoskeleton dynamics in intestinal cells? Am. J. Physiol. Gastrointest. Liver Physiol. 283(2002) G496-G502.
[40]	R.E. McConnell, M.J. Tyska, Leveraging the membrane - cytoskeleton interface with myosin-1, Trends Cell Biol. 20(2010) 418-426.
[41]	R.D. Paladini, K. Takahashi, N.S. Bravo, et al., Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16, J. Cell Biol. 132(1996) 381-397.
[42]	A. Capmany, A. Yoshimura, R. Kerdous, et al., MYO1C stabilizes actin and facilitates the arrival of transport carriers at the Golgi complex, J. Cell Sci. 132(2019), jcs225029.
[43]	J.A. Head, D. Jiang, M. Li, et al., Cortactin tyrosine phosphorylation requires Rac1 activity and association with the cortical actin cytoskeleton, Mol. Biol. Cell 14(2003) 3216-3229.
[44]	H.-N. Ye, X.-Y. Liu, B.-L. Qin, Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer. World J. Gastrointest. Oncol. 15(2023) 69-75.
[45]	E. Van Cutsem, X. Sagaert, B. Topal, et al., Gastric cancer, Lancet. 388(2016) 2654-2664.
[46]	Z. Li, G. Zhang, N. Cao, et al., Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial, Trials 23(2022), 68.
[47]	Y. Wang, F. Chu, J. Lin, et al., Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification, J. Ethnopharmacol. 279(2021), 114399.
[48]	M. Li, J. Yang, J. Li, et al., Epiberberine induced p53/p21-dependent G2/M cell cycle arrest and cell apoptosis in gastric cancer cells by activating γ-aminobutyric acid receptor- β3, Phytomedicine 123(2024), 155198.
[49]	X. Liu, K.-M. Chu, α-Actinin-4 promotes metastasis in gastric cancer, Lab. Invest. 97(2017) 1084-1094.