Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Arnicolide D Inhibits Proliferation and Induces Apoptosis of Osteosarcoma Cells through PI3K/Akt/mTOR Pathway

In Press, (this is not the final "Version of Record"). Available online 04 July, 2024
Author(s): Zhuo Chen, Renhua Ni, Yuanyu Hu, Yiyuan Yang and Yun Tian*
Published on: 04 July, 2024

DOI: 10.2174/0118715206289595240105082138

Price: $95

Abstract

Background: Osteosarcoma is considered as the most prevalent form of primary malignant bone cancer, prompting a pressing need for novel therapeutic options. Arnicolide D, a sesquiterpene lactone derived from the traditional Chinese herbal medicine Centipeda minima (known as E Bu Shi Cao in Chinese), showed anticancer efficacy against several kinds of cancers. However, its effect on osteosarcoma remains unclear.

Objective: This study aimed to investigate the anticancer activity of arnicolide D and the underlying molecular mechanism of its action in osteosarcoma cells, MG63 and U2OS.

Methods: Cell viability and proliferation were evaluated through MTT assay and colony formation assay following 24 h and 48 h treatment with different concentrations of arnicolide D. Flow cytometry was employed to examine cell cycle progression and apoptosis after 24 h treatment of arnicolide D. Western blotting was performed to determine the expression of the PI3k, Akt and m-TOR and their phosphorylated forms.

Results: Our findings revealed that arnicolide D treatment resulted in a significant reduction in cell viability, the inhibition of proliferation, and the induction of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, arnicolide D could inhibit the activation of PI3K/Akt/mTOR pathway in osteosarcoma cells.

Conclusion: Based on our results, arnicolide D demonstrated significant anti-osteosarcoma activity and held the potential to be considered as a therapeutic candidate for osteosarcoma in the future.

[1]
Taran, S.J.; Taran, R.; Malipatil, N.B. Pediatric osteosarcoma: An updated review. Indian J. Med. Paediatr. Oncol., 2017, 38(1), 33-43.
[2]
Sim, Y.C.; Hwang, J.H.; Ahn, K.M. Overall and disease-specific survival outcomes following primary surgery for oral squamous cell carcinoma: analysis of consecutive 67 patients. J. Korean Assoc. Oral Maxillofac. Surg., 2019, 45(2), 83-90.
[http://dx.doi.org/10.5125/jkaoms.2019.45.2.83] [PMID: 31106136]
[3]
Zhao, X.; Wu, Q.; Gong, X.; Liu, J.; Ma, Y. Osteosarcoma: a review of current and future therapeutic approaches. Biomed. Eng. Online, 2021, 20(1), 24.
[http://dx.doi.org/10.1186/s12938-021-00860-0] [PMID: 33653371]
[4]
Xue, W.; Zhang, Z.; Yu, H.; Li, C.; Sun, Y.; An, J.; Qi, L.; Zhang, J.; Liu, Q. Development of nomogram and discussion of radiotherapy effect for osteosarcoma survival. Sci. Rep., 2023, 13(1), 223.
[http://dx.doi.org/10.1038/s41598-023-27476-9]
[5]
Carrle, D.; Bielack, S.S. Current strategies of chemotherapy in osteosarcoma. Int. Orthop., 2006, 30(6), 445-451.
[http://dx.doi.org/10.1007/s00264-006-0192-x] [PMID: 16896870]
[6]
Zhang, Y.; Yang, J.; Zhao, N.; Wang, C.; Kamar, S.; Zhou, Y.; He, Z.; Yang, J.; Sun, B.; Shi, X.; Han, L.; Yang, Z. Progress in the chemotherapeutic treatment of osteosarcoma (Review). Oncol. Lett., 2018, 16(5), 6228-6237.
[http://dx.doi.org/10.3892/ol.2018.9434] [PMID: 30405759]
[7]
Tobeiha, M.; Rajabi, A.; Raisi, A.; Mohajeri, M.; Yazdi, S.M.; Davoodvandi, A.; Aslanbeigi, F.; Vaziri, M.; Hamblin, M.R.; Mirzaei, H. Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms. Biomed. Pharmacother., 2021, 144, 112257.
[http://dx.doi.org/10.1016/j.biopha.2021.112257] [PMID: 34688081]
[8]
Xu, C.; Wang, M.; Guo, W.; Sun, W.; Liu, Y. Curcumin in osteosarcoma therapy: Combining with immunotherapy, chemotherapeutics, bone tissue engineering materials and potential synergism with photodynamic therapy. Front. Oncol., 2021, 11, 672490.
[http://dx.doi.org/10.3389/fonc.2021.672490] [PMID: 34094974]
[9]
Tan, J.; Qiao, Z.; Meng, M.; Zhang, F.; Kwan, H.Y.; Zhong, K.; Yang, C.; Wang, Y.; Zhang, M.; Liu, Z.; Su, T. Centipeda minima: An update on its phytochemistry, pharmacology and safety. J. Ethnopharmacol., 2022, 292, 115027.
[http://dx.doi.org/10.1016/j.jep.2022.115027] [PMID: 35091011]
[10]
Lee, M.M.L.; Chan, B.D.; Wong, W.Y.; Qu, Z.; Chan, M.S.; Leung, T.W.; Lin, Y.; Mok, D.K.W.; Chen, S.; Tai, W.C.S. Anti-cancer activity of Centipeda minima extract in triple negative breast cancer via inhibition of AKT, NF-κB, and STAT3 signaling pathways. Front. Oncol., 2020, 10, 491.
[http://dx.doi.org/10.3389/fonc.2020.00491] [PMID: 32328465]
[11]
Chan, B.D.; Wong, W.Y.; Lee, M.M.L.; Leung, T.W.; Shum, T.Y.; Cho, W.C.S.; Chen, S.; Tai, W.C.S. Centipeda minima extract attenuates dextran sodium sulfate-induced acute colitis in mice by inhibiting macrophage activation and monocyte chemotaxis. Front. Pharmacol., 2021, 12, 738139.
[http://dx.doi.org/10.3389/fphar.2021.738139] [PMID: 34616300]
[12]
Pu, S.; Guo, Y.; Gao, W. Chemical constituents from Centipeda minima. Zhongguo Zhong Yao Za Zhi, 2009, 34(12), 1520-1522.
[13]
Qu, Z.; Lin, Y.; Mok, D.K.W.; Bian, Q.; Tai, W.C.S.; Chen, S.; Arnicolide, D. Arnicolide D inhibits triple negative breast cancer cell proliferation by suppression of Akt/mTOR and STAT3 signaling pathways. Int. J. Med. Sci., 2020, 17(11), 1482-1490.
[http://dx.doi.org/10.7150/ijms.46925] [PMID: 32669950]
[14]
Liu, R.; Dow Chan, B.; Mok, D.K.W.; Lee, C.S.; Tai, W.C.S.; Chen, S. Arnicolide D, from the herb Centipeda minima, is a therapeutic candidate against nasopharyngeal carcinoma. Molecules, 2019, 24(10), 1908.
[http://dx.doi.org/10.3390/molecules24101908] [PMID: 31108969]
[15]
Zhu, P.; Zheng, Z.; Fu, X.; Li, J.; Yin, C.; Chou, J.; Wang, Y.; Liu, Y.; Chen, Y.; Bai, J.; Wu, J.; Chen, S.; Yu, Z.L. Arnicolide D exerts anti-melanoma effects and inhibits the NF-κB pathway. Phytomedicine, 2019, 64, 153065.
[http://dx.doi.org/10.1016/j.phymed.2019.153065] [PMID: 31408803]
[16]
Huang, X.; Awano, Y.; Maeda, E.; Asada, Y.; Takemoto, H.; Watanabe, T.; Kojima-Yuasa, A.; Kobayashi, Y. Cytotoxic activity of two natural sesquiterpene lactones, isobutyroylplenolin and arnicolide D, on human colon cancer cell line HT-29. Nat. Prod. Res., 2014, 28(12), 914-916.
[http://dx.doi.org/10.1080/14786419.2014.889133] [PMID: 24588282]
[17]
Nik Nabil, W.N.; Xi, Z.; Liu, M.; Li, Y.; Yao, M.; Liu, T.; Dong, Q.; Xu, H. Advances in therapeutic agents targeting quiescent cancer cells. Acta Materia Medica., 2022, 1(1), 56-71.
[http://dx.doi.org/10.15212/AMM-2021-0005]
[18]
Matson, J.P.; Cook, J.G. Cell cycle proliferation decisions: the impact of single cell analyses. FEBS J., 2017, 284(3), 362-375.
[http://dx.doi.org/10.1111/febs.13898] [PMID: 27634578]
[19]
Tonami, Y.; Murakami, H.; Shirahige, K.; Nakanishi, M. A checkpoint control linking meiotic S phase and recombination initiation in fission yeast. Proc. Natl. Acad. Sci. USA, 2005, 102(16), 5797-5801.
[http://dx.doi.org/10.1073/pnas.0407236102] [PMID: 15805194]
[20]
Vassilev, L.T. Cell cycle synchronization at the G2/M phase border by reversible inhibition of CDK1. Cell Cycle, 2006, 5(22), 2555-2556.
[http://dx.doi.org/10.4161/cc.5.22.3463] [PMID: 17172841]
[21]
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[22]
Lowe, S.W.; Lin, A.W. Apoptosis in cancer. Carcinogenesis, 2000, 21(3), 485-495.
[http://dx.doi.org/10.1093/carcin/21.3.485] [PMID: 10688869]
[23]
Zhang, J.; Yu, X.H.; Yan, Y.G.; Wang, C.; Wang, W.J. PI3K/Akt signaling in osteosarcoma. Clin. Chim. Acta, 2015, 444, 182-192.
[24]
Czarnecka, A.M.; Synoradzki, K.; Firlej, W.; Bartnik, E.; Sobczuk, P.; Fiedorowicz, M.; Grieb, P.; Rutkowski, P. Molecular biology of osteosarcoma. Cancers (Basel), 2020, 12(8), 2130.
[http://dx.doi.org/10.3390/cancers12082130] [PMID: 32751922]
[25]
Hu, K.; Dai, H.B.; Qiu, Z.L. mTOR signaling in osteosarcoma: Oncogenesis and therapeutic aspects (Review). Oncol. Rep., 2016, 36(3), 1219-1225.
[http://dx.doi.org/10.3892/or.2016.4922] [PMID: 27430283]
[26]
Tewari, D.; Patni, P.; Bishayee, A.; Sah, A.N.; Bishayee, A. Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy. Semin. Cancer Biol., 2022, 80, 1-17.
[http://dx.doi.org/10.1016/j.semcancer.2019.12.008] [PMID: 31866476]
[27]
Meyer, W.H.; Malawer, M.M. Osteosarcoma. Clinical features and evolving surgical and chemotherapeutic strategies. Pediatr. Clin. North Am., 1991, 38(2), 317-348.
[http://dx.doi.org/10.1016/S0031-3955(16)38080-4] [PMID: 2006080]
[28]
Benjamin, R.S. Adjuvant and neoadjuvant chemotherapy for osteosarcoma: A historical perspective. Adv. Exp. Med. Biol., 2020, 1257, 1-10.
[http://dx.doi.org/10.1007/978-3-030-43032-0_1] [PMID: 32483726]
[29]
Lilienthal, I.; Herold, N. Targeting molecular mechanisms underlying treatment efficacy and resistance in osteosarcoma: A review of current and future strategies. Int. J. Mol. Sci., 2020, 21(18), 6885.
[http://dx.doi.org/10.3390/ijms21186885] [PMID: 32961800]
[30]
Dong, Z.; Liao, Z.; He, Y.; Wu, C.; Meng, Z.; Qin, B.; Xu, G.; Li, Z.; Sun, T.; Wen, Y.; Li, G. Advances in the biological functions and mechanisms of miRNAs in the development of osteosarcoma. Technol. Cancer Res. Treat., 2022, 21.
[http://dx.doi.org/10.1177/15330338221117386] [PMID: 35950243]
[31]
Yang, Z.; Li, X.; Yang, Y.; He, Z.; Qu, X.; Zhang, Y. Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. Cell Death Dis., 2016, 7(9), e2389.
[http://dx.doi.org/10.1038/cddis.2016.272] [PMID: 27685633]
[32]
Pistritto, G.; Trisciuoglio, D.; Ceci, C.; Garufi, A.; D’Orazi, G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY), 2016, 8(4), 603-619.
[http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]
[33]
Pang, H.; Wu, T.; Peng, Z.; Tan, Q.; Peng, X.; Zhan, Z.; Song, L.; Wei, B. Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways. J. Bone Oncol., 2022, 33, 100415.
[http://dx.doi.org/10.1016/j.jbo.2022.100415] [PMID: 35573641]
[34]
Okagu, I.U.; Ezeorba, T.P.C.; Aguchem, R.N.; Ohanenye, I.C.; Aham, E.C.; Okafor, S.N.; Bollati, C.; Lammi, C. A Review on the molecular mechanisms of action of natural products in preventing bone diseases. Int. J. Mol. Sci., 2022, 23(15), 8468.
[http://dx.doi.org/10.3390/ijms23158468] [PMID: 35955603]
[35]
Zheng, C.; Tang, F.; Min, L.; Hornicek, F.; Duan, Z.; Tu, C. PTEN in osteosarcoma: Recent advances and the therapeutic potential. Biochim. Biophys. Acta Rev. Cancer, 2020, 1874(2), 188405.
[http://dx.doi.org/10.1016/j.bbcan.2020.188405] [PMID: 32827577]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy