Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Carvacrol Suppresses Human Osteosarcoma Cells via the Wnt/β-Catenin Signaling Pathway

Author(s): Songou Zhang, Lei He, Jinxiang Shang, Long Chen, Yifan Xu, Xiaozhen Chen, Xinyu Li, Qingchuan Jiao, Songtao Jin, Xujun Hu and Wenqing Liang*

Volume 22, Issue 9, 2022

Published on: 04 January, 2022

Page: [1714 - 1722] Pages: 9

DOI: 10.2174/1871520621666210901111932

Price: $65

Abstract

Background: Carvacrol is a monoterpenic phenol extracted from traditional Chinese herbs, including oregano and thyme. Currently, carvacrol has been widely studied for its therapeutic role in central nervous system diseases, liver diseases and digestive system cancer.

Objective: However, the role of carvacrol in osteosarcoma and its underlying molecular mechanism remain elusive. Here, we aimed to examine the anticancer effects of carvacrol on osteosarcoma.

Methods: The effects of carvacrol on the osteosarcoma proliferation capacity were revealed by CCK-8 and colony formation assays. Flow cytometry and Hoechst assays were used to determine the effects of carvacrol on osteosarcoma cell apoptosis. The effect of carvacrol on migration and invasion of osteosarcoma cells was determined by wound healing and transwell tests. Protein expression was evaluated by WB assays. The suppressive effects of carvacrol on osteosarcoma in vivo were examined by a xenograft animal model, immunohistochemistry and HE staining.

Results: We demonstrated that carvacrol treatment reduced viability and inhibited the colony formation of U2OS and 143B cells in a concentration-dependent manner. Apoptotic cell number increased after exposure to carvacrol. Meanwhile, the expression of Bax increased, and that of Bcl-2 decreased by carvacrol treatment. In addition, the MMP-9 expression and migration and invasion of 143B and U2OS cells were inhibited by carvacrol. We also found that these carvacrol-induced effects on osteosarcoma are associated with the regulation of the Wnt/β-catenin signaling pathway.

Conclusion: Our findings suggest that carvacrol suppresses proliferation, migration, invasion and promotes apoptosis in osteosarcoma cells, in part by regulating the Wnt/β-catenin signaling pathway.

Keywords: Carvacrol, osteosarcoma, Wnt/β-catenin signaling pathway, metastasis, anticancer effects, apoptosis.

Graphical Abstract
[1]
Ottaviani, G.; Jaffe, N. The epidemiology of osteosarcoma. Cancer Treat. Res.,; , 2009, 152, pp. 3-13.
[http://dx.doi.org/10.1007/978-1-4419-0284-9_1] [PMID: 20213383]
[2]
Kager, L.; Tamamyan, G.; Bielack, S. Novel insights and therapeutic interventions for pediatric osteosarcoma. Future Oncol., 2017, 13(4), 357-368.
[http://dx.doi.org/10.2217/fon-2016-0261] [PMID: 27651036]
[3]
Moore, D.D.; Luu, H.H. Osteosarcoma. Cancer Treat. Res , 2014; 162, pp. 65-92.
[http://dx.doi.org/10.1007/978-3-319-07323-1_4] [PMID: 25070231]
[4]
Singla, A.; Wang, J.; Yang, R.; Geller, D.S.; Loeb, D.M.; Hoang, B.H. Wnt signaling in osteosarcoma. Adv. Exp. Med. Biol., 2020, 1258, 125-139.
[http://dx.doi.org/10.1007/978-3-030-43085-6_8] [PMID: 32767238]
[5]
Zhang, H.; Yan, J.; Lang, X.; Zhuang, Y. Expression of circ_001569 is upregulated in osteosarcoma and promotes cell proliferation and cisplatin resistance by activating the Wnt/β-catenin signaling pathway. Oncol. Lett., 2018, 16(5), 5856-5862.
[http://dx.doi.org/10.3892/ol.2018.9410] [PMID: 30344736]
[6]
Patel, S.; Alam, A.; Pant, R.; Chattopadhyay, S. Wnt signaling and its significance within the tumor microenvironment: Novel therapeutic insights. Front. Immunol., 2019, 10, 2872.
[http://dx.doi.org/10.3389/fimmu.2019.02872] [PMID: 31921137]
[7]
Khan, F.; Singh, V.K.; Saeed, M.; Kausar, M.A.; Ansari, I.A. Carvacrol induced program cell death and cell cycle arrest in androgen-independent human prostate cancer cells via inhibition of notch signaling. Anticancer. Agents Med. Chem., 2019, 19(13), 1588-1608.
[http://dx.doi.org/10.2174/1871520619666190731152942] [PMID: 31364516]
[8]
Trindade, GGG.; Thrivikraman, G.; Menezes, PP.; França, CM.; Lima, B.S.; Carvalho, YMBG.; Souza, EPBSS.; Duarte, MC.; Shanmugam, S.; Quintans-Júnior, LJ.; Bezerra, DP.; Bertassoni, LE; Araújo, AAS. Carvacrol/β-cyclodextrin inclusion complex inhibits cell proliferation and migration of prostate cancer cells. Food Chem. Toxicol.: Published for the Briti. Indust. Biolo. Res. Associ., 2019, 125, 198-209.
[9]
Jung, C.Y.; Kim, S.Y.; Lee, C. Carvacrol targets AXL to inhibit cell proliferation and migration in non-small cell lung cancer cells. Anticancer Res., 2018, 38(1), 279-286.
[PMID: 29277784]
[10]
Dai, W.; Sun, C.; Huang, S.; Zhou, Q. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma. OncoTargets Ther., 2016, 9, 2297-2304.
[http://dx.doi.org/10.2147/OTT.S98875] [PMID: 27143925]
[11]
Ezz-Eldin, Y.M.; Aboseif, A.A.; Khalaf, M.M. Potential anti-inflammatory and immunomodulatory effects of carvacrol against ovalbumin-induced asthma in rats. Life Sci., 2020, 242, 117222.
[http://dx.doi.org/10.1016/j.lfs.2019.117222] [PMID: 31881223]
[12]
Gilling, D.H.; Kitajima, M.; Torrey, J.R.; Bright, K.R. Antiviral efficacy and mechanisms of action of oregano essential oil and its primary component carvacrol against murine norovirus. J. Appl. Microbiol., 2014, 116(5), 1149-1163.
[http://dx.doi.org/10.1111/jam.12453] [PMID: 24779581]
[13]
Dati, L.M.; Ulrich, H.; Real, C.C.; Feng, Z.P.; Sun, H.S.; Britto, L.R. Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience, 2017, 356, 176-181.
[http://dx.doi.org/10.1016/j.neuroscience.2017.05.013] [PMID: 28526576]
[14]
Marchese, A.; Arciola, C.R.; Coppo, E.; Barbieri, R.; Barreca, D.; Chebaibi, S.; Sobarzo-Sánchez, E.; Nabavi, S.F.; Nabavi, S.M.; Daglia, M. The natural plant compound carvacrol as an antimicrobial and anti-biofilm agent: mechanisms, synergies and bio-inspired anti-infective materials. Biofouling, 2018, 34(6), 630-656.
[http://dx.doi.org/10.1080/08927014.2018.1480756] [PMID: 30067078]
[15]
Heidarian, E.; Keloushadi, M. Antiproliferative and anti-invasion effects of carvacrol on PC3 human prostate cancer cells through reducing pSTAT3, pAKT, and pERK1/2 signaling proteins. Int. J. Prev. Med., 2019, 10, 156.
[http://dx.doi.org/10.4103/ijpvm.IJPVM_292_17] [PMID: 32133074]
[16]
Jamali, T.; Kavoosi, G.; Ardestani, S.K. In-vitro and in-vivo anti-breast cancer activity of OEO (Oliveria decumbens vent essential oil) through promoting the apoptosis and immunomodulatory effects. J. Ethnopharmacol., 2020, 248, 112313.
[http://dx.doi.org/10.1016/j.jep.2019.112313] [PMID: 31655147]
[17]
Fan, K.; Li, X.; Cao, Y.; Qi, H.; Li, L.; Zhang, Q.; Sun, H. Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells. Anticancer Drugs, 2015, 26(8), 813-823.
[http://dx.doi.org/10.1097/CAD.0000000000000263] [PMID: 26214321]
[18]
Potočnjak, I.; Gobin, I.; Domitrović, R. Carvacrol induces cytotoxicity in human cervical cancer cells but causes cisplatin resistance: Involvement of MEK-ERK activation. Phytother. Res., 2018, 32(6), 1090-1097.
[http://dx.doi.org/10.1002/ptr.6048] [PMID: 29417642]
[19]
Maryam, K.; Shakeri, S.; Kiani, K. Preparation and in vitro investigation of antigastric cancer activities of carvacrol-loaded human serum albumin nanoparticles. IET nanobiotechnology,, 2015, 9(5), 294-299.
[http://dx.doi.org/10.1049/iet-nbt.2014.0040]
[20]
Elbe, H.; Yigitturk, G.; Cavusoglu, T.; Baygar, T.; Ozgul Onal, M.; Ozturk, F. Comparison of ultrastructural changes and the anticarcinogenic effects of thymol and carvacrol on ovarian cancer cells: which is more effective? Ultrastruct. Pathol., 2020, 44(2), 193-202.
[http://dx.doi.org/10.1080/01913123.2020.1740366] [PMID: 32183603]
[21]
Khan, I.; Bahuguna, A.; Kumar, P.; Bajpai, V.K.; Kang, S.C. In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis. Sci. Rep., 2018, 8(1), 144.
[http://dx.doi.org/10.1038/s41598-017-18644-9] [PMID: 29317755]
[22]
Lim, W.; Ham, J.; Bazer, F.W.; Song, G. Carvacrol induces mitochondria-mediated apoptosis via disruption of calcium homeostasis in human choriocarcinoma cells. J. Cell. Physiol., 2019, 234(2), 1803-1815.
[http://dx.doi.org/10.1002/jcp.27054] [PMID: 30070691]
[23]
Pastushenko, I.; Blanpain, C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol., 2019, 29(3), 212-226.
[http://dx.doi.org/10.1016/j.tcb.2018.12.001] [PMID: 30594349]
[24]
Jiang, X.; Zhang, Z.; Song, C.; Deng, H.; Yang, R.; Zhou, L.; Sun, Y.; Zhang, Q. Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Chem. Biol. Interact., 2019, 307, 158-166.
[http://dx.doi.org/10.1016/j.cbi.2019.05.005] [PMID: 31059706]
[25]
Qiu, J.; Zhang, Y.; Chen, H.; Guo, Z. MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3. Int. J. Oncol., 2018, 53(4), 1493-1504.
[http://dx.doi.org/10.3892/ijo.2018.4483] [PMID: 30015825]
[26]
Fang, F.; VanCleave, A.; Helmuth, R.; Torres, H.; Rickel, K.; Wollenzien, H.; Sun, H.; Zeng, E.; Zhao, J.; Tao, J. Targeting the Wnt/β-catenin pathway in human osteosarcoma cells. Oncotarget, 2018, 9(95), 36780-36792.
[http://dx.doi.org/10.18632/oncotarget.26377] [PMID: 30613366]
[27]
Li, X.; Lu, Q.; Xie, W.; Wang, Y.; Wang, G. Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/β-Catenin signaling. Biochem. Biophys. Res. Commun., 2018, 496(2), 443-449.
[http://dx.doi.org/10.1016/j.bbrc.2018.01.052] [PMID: 29330051]
[28]
Lee, E.H.; Chun, S.Y.; Kim, B.; Yoon, B.H.; Lee, J.N.; Kim, B.S.; Yoo, E.S.; Lee, S.; Song, P.H.; Kwon, T.G.; Ha, Y.S. Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer. BMC Urol., 2020, 20(1), 145.
[http://dx.doi.org/10.1186/s12894-020-00714-2] [PMID: 32907556]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy