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Anti-Cancer Agents in Medicinal Chemistry

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

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Research Article

Arnicolide D Inhibits Oxidative Stress-induced Breast Cancer Cell Growth and Invasion through Apoptosis, Ferroptosis, and Parthanatos

Author(s): Wei Wen*, Ke Jin, Ying Che, Lin-Yao Du and Li-Na Wang

Volume 24, Issue 11, 2024

Published on: 15 April, 2024

Page: [836 - 844] Pages: 9

DOI: 10.2174/1871520623666221208102021

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Abstract

Background: Breast cancer is the most common malignant tumor in women, and its pathogenesis is very complicated. More and more studies have found that Traditional Chinese Medicine plays an important role in tumor prevention.

Objective: To investigate the mechanism of arnicolide D isolated from Centipeda minima in breast cancer.

Methods: Cell Counting Kit-8 (CCK-8), western blot, RT-qPCR, ELISA, flow cytometry, and Transwell were used to detect the effect of arnicolide D on the biological function of breast cancer cells.

Results: Arnicolide D promoted reactive oxygen species (ROS) production and induced a decrease in mitochondrial membrane potential in breast cancer cells, thereby inhibiting cell viability and increasing lactate dehydrogenase (LDH) release. Arnicolide D activated the classical apoptosis pathway to induce cell apoptosis; it significantly promoted PARP-1 expression, enhanced the nuclear translocation of apoptosis-inducing factor (AIF), and reduced the expression of AIF in mitochondria, indicating that it can induce the occurrence of parthanatos in a ROS dependent manner. In addition, arnicolide D down-regulated glutathione peroxidase 4 (GPX4) expression and increased the accumulation of Fe2+ and malondialdehyde (MDA), thereby activating ferroptosis. Apoptosis inhibitor, ferroptosis inhibitor, PARP inhibitor, PARP-1 siRNA, AIF siRNA and GPX4 overexpression vector significantly attenuated the inhibitory effect of arnicolide D on cell viability and reduced LDH release, which indicates that arnicolide D inhibits breast cancer cell growth by inducing apoptosis, parthanatos and ferroptosis. Arnicolide D also reduced breast cancer cell invasion and inhibited the expression of matrix metallopeptidase (MMP)-2 and MMP-9.

Conclusion: Arnicolide D can activate a variety of cell death modes by inducing oxidative stress, thereby inhibiting the growth and invasion of breast cancer cells, indicating that arnicolide D has a good anti-tumor effect.

Keywords: Breast cancer, chinese medicinal herb, arnicolide D, ferroptosis, parthanatos, reactive oxygen species (ROS).

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[1]
Ghoncheh, M.; Pournamdar, Z.; Salehiniya, H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac. J. Cancer Prev., 2016, 17(sup3), 43-46.
[http://dx.doi.org/10.7314/APJCP.2016.17.S3.43] [PMID: 27165206]
[2]
Fahad, U.M. Breast cancer: Current perspectives on the disease status. Adv. Exp. Med. Biol., 2019, 1152, 51-64.
[http://dx.doi.org/10.1007/978-3-030-20301-6_4] [PMID: 31456179]
[3]
Hussain, Y.; Islam, L.; Khan, H.; Filosa, R.; Aschner, M.; Javed, S. Curcumin–cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytother. Res., 2021, 35(12), 6514-6529.
[http://dx.doi.org/10.1002/ptr.7225] [PMID: 34347326]
[4]
Man, S.; Gao, W.; Wei, C.; Liu, C. Anticancer drugs from traditional toxic Chinese medicines. Phytother. Res., 2012, 26(10), 1449-1465.
[http://dx.doi.org/10.1002/ptr.4609] [PMID: 22389143]
[5]
Linh, N.T.T.; Ha, N.T.T.; Tra, N.T.; Anh, L.T.T.; Tuyen, N.V.; Son, N.T. Medicinal plant Centipeda Minima: A resource of bioactive compounds. Mini Rev. Med. Chem., 2021, 21(3), 273-287.
[http://dx.doi.org/10.2174/1389557520666201021143257] [PMID: 33087028]
[6]
Khan, M.; Maryam, A.; Saleem, M.Z.; Shakir, H.A.; Qazi, J.I.; Li, Y.; Ma, T. Brevilin A induces ROS-dependent apoptosis and suppresses STAT3 activation by direct binding in human lung cancer cells. J. Cancer, 2020, 11(13), 3725-3735.
[http://dx.doi.org/10.7150/jca.40983] [PMID: 32328177]
[7]
Gupta, R.K.; Patel, A.K.; Shah, N.; Choudhary, A.K.; Jha, U.K.; Yadav, U.C.; Gupta, P.K.; Pakuwal, U. Oxidative stress and antioxidants in disease and cancer: A review. Asian Pac. J. Cancer Prev., 2014, 15(11), 4405-4409.
[http://dx.doi.org/10.7314/APJCP.2014.15.11.4405] [PMID: 24969860]
[8]
Kim, J.H.; Kim, J.; Roh, J.; Park, C.S.; Seoh, J.Y.; Hwang, E.S. Reactive oxygen species-induced parthanatos of immunocytes by human cytomegalovirus-associated substance. Microbiol. Immunol., 2018, 62(4), 229-242.
[http://dx.doi.org/10.1111/1348-0421.12575] [PMID: 29350405]
[9]
Su, L.J.; Zhang, J.H.; Gomez, H.; Murugan, R.; Hong, X.; Xu, D.; Jiang, F.; Peng, Z.Y. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid. Med. Cell. Longev., 2019, 2019, 1-13.
[http://dx.doi.org/10.1155/2019/5080843] [PMID: 31737171]
[10]
Zhou, Y.; Liu, L.; Tao, S.; Yao, Y.; Wang, Y.; Wei, Q.; Shao, A.; Deng, Y. Parthanatos and its associated components: Promising therapeutic targets for cancer. Pharmacol. Res., 2021, 163, 105299.
[http://dx.doi.org/10.1016/j.phrs.2020.105299] [PMID: 33171306]
[11]
Galia, A.; Calogero, A.E.; Condorelli, R.; Fraggetta, F.; La Corte, A.; Ridolfo, F.; Bosco, P.; Castiglione, R.; Salemi, M. PARP-1 protein expression in glioblastoma multiforme. Eur. J. Histochem., 2012, 56(1), 9.
[http://dx.doi.org/10.4081/ejh.2012.e9] [PMID: 22472897]
[12]
Li, J.; Cao, F.; Yin, H.; Huang, Z.; Lin, Z.; Mao, N.; Sun, B.; Wang, G. Ferroptosis: Past, present and future. Cell Death Dis., 2020, 11(2), 88.
[http://dx.doi.org/10.1038/s41419-020-2298-2] [PMID: 32015325]
[13]
Lee, M.M.L.; Chan, B.D.; Wong, W.Y.; Leung, T.W.; Qu, Z.; Huang, J.; Zhu, L.; Lee, C.S.; Chen, S.; Tai, W.C.S. Synthesis and evaluation of novel anticancer compounds derived from the natural product brevilin A. ACS Omega, 2020, 5(24), 14586-14596.
[http://dx.doi.org/10.1021/acsomega.0c01276] [PMID: 32596596]
[14]
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]
[15]
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]
[16]
Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med., 2019, 8(5), 1958-1975.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[17]
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]
[18]
Yu, H.J.; Jung, J.Y.; Jeong, J.H.; Cho, S.D.; Lee, J.S. Induction of apoptosis by parthenolide in human oral cancer cell lines and tumor xenografts. Oral Oncol., 2015, 51(6), 602-609.
[http://dx.doi.org/10.1016/j.oraloncology.2015.03.003] [PMID: 25817195]
[19]
Chen, C.N.; Huang, H.H.; Wu, C.L.; Lin, C.P.C.; Hsu, J.T.A.; Hsieh, H.P.; Chuang, S.E.; Lai, G.M. Isocostunolide, a sesquiterpene lactone, induces mitochondrial membrane depolarization and caspase-dependent apoptosis in human melanoma cells. Cancer Lett., 2007, 246(1-2), 237-252.
[http://dx.doi.org/10.1016/j.canlet.2006.03.004] [PMID: 16697106]
[20]
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]
[21]
Park, E.J.; Min, K.; Lee, T-J.; Yoo, Y.H.; Kim, Y-S.; Kwon, T.K. β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells. Cell Death Dis., 2014, 5(5), e1230.
[http://dx.doi.org/10.1038/cddis.2014.202] [PMID: 24832602]
[22]
Ma, D.; Lu, B.; Feng, C.; Wang, C.; Wang, Y.; Luo, T.; Feng, J.; Jia, H.; Chi, G.; Luo, Y.; Ge, P. Deoxypodophyllotoxin triggers parthanatos in glioma cells via induction of excessive ROS. Cancer Lett., 2016, 371(2), 194-204.
[http://dx.doi.org/10.1016/j.canlet.2015.11.044] [PMID: 26683770]
[23]
Batnasan, E.; Wang, R.; Wen, J.; Ke, Y.; Li, X.; Bohio, A.A.; Zeng, X.; Huo, H.; Han, L.; Boldogh, I.; Ba, X. 17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha. Toxicol. Lett., 2015, 232(1), 1-9.
[http://dx.doi.org/10.1016/j.toxlet.2014.09.024] [PMID: 25280774]
[24]
Li, Z.; Chen, L.; Chen, C.; Zhou, Y.; Hu, D.; Yang, J.; Chen, Y.; Zhuo, W.; Mao, M.; Zhang, X.; Xu, L.; Wang, L.; Zhou, J. Targeting ferroptosis in breast cancer. Biomark. Res., 2020, 8(1), 58.
[http://dx.doi.org/10.1186/s40364-020-00230-3] [PMID: 33292585]
[25]
Ma, S.; Henson, E.S.; Chen, Y.; Gibson, S.B. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis., 2016, 7(7), e2307.
[http://dx.doi.org/10.1038/cddis.2016.208] [PMID: 27441659]
[26]
Mbaveng, A.T.; Bitchagno, G.T.M.; Kuete, V.; Tane, P.; Efferth, T. Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy. Phytomedicine, 2019, 60, 152832.
[http://dx.doi.org/10.1016/j.phymed.2019.152832] [PMID: 31031043]

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