Curcumol Inhibits Malignant Biological Behaviors and TMZ-resistance in Glioma Cells by Inhibiting Long Noncoding RNA FOXD2-As1-promoted EZH2 Activation

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Nov 5

PMID 34739394

Citations 5

Authors

Xuyang Lv

Jiangchuan Sun

Linfeng Hu

Ying Qian

Chunlei Fan

Nan Tian

Affiliations

Soon will be listed here.

Abstract

Currently, conventional treatment is not sufficient to improve the survival of glioma patients. Hence, adopting novel personalized treatment programs is imperative. Curcumol, a Chinese herbal medicine extract from the roots of , has attracted significant interest due to its beneficial pharmacological activities. The current study revealed that curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance in glioma cells and . Next, the potential molecular mechanisms of curcumol in inhibiting glioma were investigated. We found that the long non-coding RNA (lncRNA) FOXD2-As1 might contribute to the effects of curcumol on glioma cells. Enforced expression of FOXD2-As1 attenuated the curcumol-induced reduction in glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-As1 reversed the inhibitory effect of curcumol on the binding ability of EZH2 and H3K27me3 modification in the promoter regions of anti-oncogenes. Our results showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-As1-mediated EZH2 activation. Our study offers the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

Citing Articles

[Curcumol reverses temozolomide resistance in glioma cells by regulating the UTX/MGMT axis].

Sun J, Xing J, Tan R, Qian Y, Tian N Nan Fang Yi Ke Da Xue Xue Bao. 2023; 43(10):1697-1705.

PMID: 37933645 PMC: 10630207. DOI: 10.12122/j.issn.1673-4254.2023.10.07.

Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma.

Tan C, Wei J, Li Z, Tian N, Wang Z, Wang G BMC Cancer. 2023; 23(1):808.

PMID: 37644421 PMC: 10463850. DOI: 10.1186/s12885-023-11263-w.

Cincumol prevents malignant phenotype of colorectal cancer cell line HCT116 via inhibiting PI3K/AKT signaling in vitro.

Hu G, Chen W, Peng W, Huang Z, Dong Z, Cao Y Acta Cir Bras. 2023; 37(12):e371201.

PMID: 36651426 PMC: 9839155. DOI: 10.1590/acb371201.

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages.

Wang J, Jin J, Chen T, Zhou Q Molecules. 2022; 27(14).

PMID: 35889217 PMC: 9318016. DOI: 10.3390/molecules27144345.

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review).

Zeng Z, Chen Y, Geng X, Zhang Y, Wen X, Yan Q Int J Oncol. 2022; 60(6).

PMID: 35506469 PMC: 9083885. DOI: 10.3892/ijo.2022.5366.

References

Yang Y, Islam M, Wang J, Li Y, Chen X . Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int J Biol Sci. 2020; 16(10):1708-1717. PMC: 7098036. DOI: 10.7150/ijbs.45538. View

Ning N, Liu S, Liu X, Tian Z, Jiang Y, Yu N . Curcumol inhibits the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways. J Cancer. 2020; 11(7):1679-1692. PMC: 7052881. DOI: 10.7150/jca.38624. View

Ma X, Yu M, Hao C, Yang W . Shikonin induces tumor apoptosis in glioma cells via endoplasmic reticulum stress, and Bax/Bak mediated mitochondrial outer membrane permeability. J Ethnopharmacol. 2020; 263:113059. DOI: 10.1016/j.jep.2020.113059. View

Yu T, Wang Y, Hu Q, Wu W, Wu Y, Wei W . The EZH2 inhibitor GSK343 suppresses cancer stem-like phenotypes and reverses mesenchymal transition in glioma cells. Oncotarget. 2017; 8(58):98348-98359. PMC: 5716734. DOI: 10.18632/oncotarget.21311. View

Shangguan W, Lv X, Tian N . is a prognostic factor in glioma and promotes temozolomide resistance in a O-methylguanine-DNA methyltransferase-dependent manner. Korean J Physiol Pharmacol. 2019; 23(6):475-482. PMC: 6819902. DOI: 10.4196/kjpp.2019.23.6.475. View

Shen F, Chang H, Gao G, Zhang B, Li X, Jin B . Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis. J Cell Biochem. 2018; 120(6):9324-9336. DOI: 10.1002/jcb.28208. View

Chua J, Nafziger E, Leung D . Evidence-Based Practice: Temozolomide Beyond Glioblastoma. Curr Oncol Rep. 2019; 21(4):30. DOI: 10.1007/s11912-019-0783-5. View

Zhou L, Wei E, Zhou B, Bi G, Gao L, Zhang T . Anti-proliferative benefit of curcumol on human bladder cancer cells via inactivating EZH2 effector. Biomed Pharmacother. 2018; 104:798-805. DOI: 10.1016/j.biopha.2018.05.101. View

Nakagawa S, Okabe H, Ouchi M, Tokunaga R, Umezaki N, Higashi T . Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma. HPB (Oxford). 2018; 20(10):939-948. DOI: 10.1016/j.hpb.2018.03.018. View

10.

Wang D, Calabrese E, Lian B, Lin Z, Calabrese V . Hormesis as a mechanistic approach to understanding herbal treatments in traditional Chinese medicine. Pharmacol Ther. 2017; 184:42-50. DOI: 10.1016/j.pharmthera.2017.10.013. View

11.

Zuo H, Jin Y, Wang Z, Li M, Zhang Z, Wang J . Curcumol inhibits the expression of programmed cell death-ligand 1 through crosstalk between hypoxia-inducible factor-1α and STAT3 (T705) signaling pathways in hepatic cancer. J Ethnopharmacol. 2020; 257:112835. DOI: 10.1016/j.jep.2020.112835. View

12.

Yin G, Cheng X, Tao W, Dong Y, Bian Y, Zang W . Comparative analysis of multiple representative components in the herb pair Astragali Radix-Curcumae Rhizoma and its single herbs by UPLC-QQQ-MS. J Pharm Biomed Anal. 2017; 148:224-229. DOI: 10.1016/j.jpba.2017.09.015. View

13.

You S, He X, Wang M, Mao L, Zhang L . Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-1 (TLN1) Axis. Cancer Manag Res. 2020; 12:11309-11320. PMC: 7654526. DOI: 10.2147/CMAR.S256347. View

14.

Scheid V, Tuffrey V, Weijburg T, Bovey M, Ward T . Chinese medicine treatment for menopausal symptoms in the UK health service: is a clinical trial warranted?. Maturitas. 2014; 80(2):179-86. DOI: 10.1016/j.maturitas.2014.11.006. View

15.

Li P, Chen S, Xiangfei D, Mao C, Wu C, Shih J . PAMs inhibits monoamine oxidase a activity and reduces glioma tumor growth, a potential adjuvant treatment for glioma. BMC Complement Med Ther. 2020; 20(1):252. PMC: 7429690. DOI: 10.1186/s12906-020-03041-z. View

16.

Ren Z, Hu Y, Li G, Kang Y, Liu Y, Zhao H . HIF-1α induced long noncoding RNA FOXD2-AS1 promotes the osteosarcoma through repressing p21. Biomed Pharmacother. 2019; 117:109104. DOI: 10.1016/j.biopha.2019.109104. View

17.

Ni W, Xia Y, Bi Y, Wen F, Hu D, Luo L . FoxD2-AS1 promotes glioma progression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway. Aging (Albany NY). 2019; 11(5):1427-1439. PMC: 6428107. DOI: 10.18632/aging.101843. View

18.

Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P . Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002; 298(5595):1039-43. DOI: 10.1126/science.1076997. View

19.

Liu Y, Fan H, Ding J, Huang C, Deng S, Zhu T . Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines. Sci Rep. 2017; 7:46654. PMC: 5402396. DOI: 10.1038/srep46654. View

20.

LaPointe S, Perry A, Butowski N . Primary brain tumours in adults. Lancet. 2018; 392(10145):432-446. DOI: 10.1016/S0140-6736(18)30990-5. View