Arnicolide D Inhibits Oxidative Stress-induced Breast Cancer Cell Growth and Invasion through Apoptosis, Ferroptosis, and Parthanatos
- Authors: Wen W.1, Jin K.2, Che Y.3, Du L.3, Wang L.3
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Affiliations:
- General Surgery Department, the First Affiliated Hospital of Dalian Medical University
- Emergency Department, the second Affiliated Hospital of Dalian Medical University
- Ultrasonic Diagnostics Department, The First Affiliated Hospital of Dalian Medical University
- Issue: Vol 24, No 11 (2024)
- Pages: 836-844
- Section: Oncology
- URL: https://rjsocmed.com/1871-5206/article/view/643741
- DOI: https://doi.org/10.2174/1871520623666221208102021
- ID: 643741
Cite item
Full Text
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.
About the authors
Wei Wen
General Surgery Department, the First Affiliated Hospital of Dalian Medical University
Author for correspondence.
Email: info@benthamscience.net
Ke Jin
Emergency Department, the second Affiliated Hospital of Dalian Medical University
Email: info@benthamscience.net
Ying Che
Ultrasonic Diagnostics Department, The First Affiliated Hospital of Dalian Medical University
Email: info@benthamscience.net
Lin-Yao Du
Ultrasonic Diagnostics Department, The First Affiliated Hospital of Dalian Medical University
Email: info@benthamscience.net
Li-Na Wang
Ultrasonic Diagnostics Department, The First Affiliated Hospital of Dalian Medical University
Email: info@benthamscience.net
References
- 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. doi: 10.7314/APJCP.2016.17.S3.43 PMID: 27165206
- Fahad, U.M. Breast cancer: Current perspectives on the disease status. Adv. Exp. Med. Biol., 2019, 1152, 51-64. doi: 10.1007/978-3-030-20301-6_4 PMID: 31456179
- Hussain, Y.; Islam, L.; Khan, H.; Filosa, R.; Aschner, M.; Javed, S. Curcumincisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytother. Res., 2021, 35(12), 6514-6529. doi: 10.1002/ptr.7225 PMID: 34347326
- Man, S.; Gao, W.; Wei, C.; Liu, C. Anticancer drugs from traditional toxic Chinese medicines. Phytother. Res., 2012, 26(10), 1449-1465. doi: 10.1002/ptr.4609 PMID: 22389143
- 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. doi: 10.2174/1389557520666201021143257 PMID: 33087028
- 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. doi: 10.7150/jca.40983 PMID: 32328177
- 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. doi: 10.7314/APJCP.2014.15.11.4405 PMID: 24969860
- 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. doi: 10.1111/1348-0421.12575 PMID: 29350405
- 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. doi: 10.1155/2019/5080843 PMID: 31737171
- 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. doi: 10.1016/j.phrs.2020.105299 PMID: 33171306
- 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. doi: 10.4081/ejh.2012.e9 PMID: 22472897
- 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. doi: 10.1038/s41419-020-2298-2 PMID: 32015325
- 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. doi: 10.1021/acsomega.0c01276 PMID: 32596596
- 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. doi: 10.1016/j.phymed.2019.153065 PMID: 31408803
- 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. doi: 10.3390/molecules24101908 PMID: 31108969
- 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. doi: 10.1002/cam4.2108 PMID: 30945475
- 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. doi: 10.7150/ijms.46925 PMID: 32669950
- 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. doi: 10.1016/j.oraloncology.2015.03.003 PMID: 25817195
- 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. doi: 10.1016/j.canlet.2006.03.004 PMID: 16697106
- 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. doi: 10.1080/14786419.2014.889133 PMID: 24588282
- 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. doi: 10.1038/cddis.2014.202 PMID: 24832602
- 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. doi: 10.1016/j.canlet.2015.11.044 PMID: 26683770
- 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. doi: 10.1016/j.toxlet.2014.09.024 PMID: 25280774
- 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. doi: 10.1186/s40364-020-00230-3 PMID: 33292585
- 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. doi: 10.1038/cddis.2016.208 PMID: 27441659
- 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. doi: 10.1016/j.phymed.2019.152832 PMID: 31031043
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