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Pediatric Surgery International

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01-12-2023 | Neuroblastoma | Original Article

Polyphyllin D induces necroptosis in neuroblastoma cells (IMR-32 and LA-N-2) in mice

Authors: Shunsuke Watanabe, Mikihiro Inoue, Tatsuya Suzuki, Yasuhiro Kondo, Mika Murayama

Published in: Pediatric Surgery International | Issue 1/2023

Abstract

Background

We previously reported that polyphyllin D, the main component of the traditional herbal medicinal Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine in vivo antitumor effects of polyphyllin D.

Methods

Subcutaneous tumors were established in immune-deficient BALB/c nude mice using human neuroblastoma cell lines IMR-32 and LA-N-2. To evaluate the polyphyllin D activity, we used a mouse model of IMR-32 or LA-N-2 cell lines and analyzed subcutaneous tumors.

Results

Subcutaneous tumor models were successfully established in mice using two human neuroblastoma cell lines. In the subcutaneous tumor model, porphyrin D was found to suppress tumor volume. We found that polyphyllin D suppressed the number of foci by Ki-67 staining (IMR-32 and LA-N-2; p < 0.01, 0.02, respectively). We found that polyphyllin D induces the RIPK3 expression, while polyphyllin D phosphorylates Ser358 in IMR-32 and Ser358 and Tyr376 in LA-N-2.

Conclusion

We developed a mouse model of subcutaneous tumors of neuroblastoma and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma. Polyphyllin D can cause necroptosis depending on the cell type. The new drug can be expected by investigating a method to selectively induce cell death through the analysis of necroptosis.

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Maris JM, Hogarty MD, Bagatell R et al (2007) Neuroblastoma. Lancet 369:2106–2120. https://doi.org/10.1016/S0140-6736(07)60983-0CrossRefPubMed

Ohira M, Nakamura Y, Takimoto T et al (2021) Retrospective analysis of INRG clinical and genomic factors for 605 neuroblastomas in Japan: a report from the Japan Children’s Cancer Group neuroblastoma committee (JCCG-JNBSG). Biomolecules. https://doi.org/10.3390/biom12010018CrossRefPubMedPubMedCentral

DuBois SG, Macy ME, Henderson TO (2022) High-risk and relapsed neuroblastoma: toward more cures and better outcomes. Am Soc Clin Oncol Educ Book 42:1–13. https://doi.org/10.1200/EDBK_349783CrossRefPubMed

Siripuram R, Bartolek Z, Patil K et al (2022) Disruption of colorectal cancer network by polyphyllins reveals pivotal entities with implications for chemoimmunotherapy. Biomedicines 10(10):583. https://doi.org/10.3390/biomedicines10030583CrossRefPubMedPubMedCentral

Liu Z, Zheng Q, Chen W et al (2017) Chemosensitizing effect of Paris Saponin I on camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways. Eur J Med Chem 125:760–769. https://doi.org/10.1016/j.ejmech.2016.09.066CrossRefPubMed

Gu L, Feng J, Zheng Z et al (2016) Polyphyllin I inhibits the growth of ovarian cancer cells in nude mice. Oncol Lett 12:4969–4974. https://doi.org/10.3892/ol.2016.5348CrossRefPubMedPubMedCentral

Cheung JY, Ong RC, Suen YK et al (2005) Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells. Cancer Lett 217:20311. https://doi.org/10.1016/j.canlet.2004.06.042CrossRef

Yu Q, Li Q, Lu P, Chen Q (2014) Polyphyllin D induces apoptosis in U87 human glioma cells through the c-Jun NH2-terminal kinase pathway. J Med Food 17:1036–1042. https://doi.org/10.1089/jmf.2013.2957CrossRefPubMed

Liang Y, Li X, He X et al (2016) Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating beta-catenin signaling pathway. Eur J Haematol 97:371–378. https://doi.org/10.1111/ejh.12741CrossRefPubMed

10.

Watanabe S, Suzuki T, Hara F et al (2017) Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells. Pediatr Surg Int 33:713–719. https://doi.org/10.1007/s00383-017-4069-4CrossRefPubMed

11.

Wang H, Sun L, Su L et al (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54:133–146. https://doi.org/10.1016/j.molcel.2014.03.003CrossRefPubMed

12.

Jiang H, Zhao PJ, Su D et al (2014) Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo. Mol Med Rep 9:2265–2272. https://doi.org/10.3892/mmr.2014.2108CrossRefPubMed

13.

Khurana KK, Xu W, Wang D et al (2015) Rapid on-site evaluation with dynamic telecytopathology for ultrasound-guided fine-needle aspiration of head and neck nonthyroid lesions. J Pathol Inform 6:19. https://doi.org/10.4103/2153-3539.157781CrossRefPubMedPubMedCentral

14.

Watanabe S, Suzuki T, Kondo Y et al (2019) Evaluation of Ki-67 as prognostic factor for pediatric neuroblastoma and the possibility of molecular-targeted drugs with vascular endothelial growth factor and platelet-derived growth factor receptor. Minerva Pediatr. https://doi.org/10.23736/S0026-4946.18.05444-0CrossRef

15.

Kimani SG, Kumar S, Davra V et al (2016) Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase. Cell Commun Signal 14:19. https://doi.org/10.1186/s12964-016-0142-1CrossRefPubMedPubMedCentral

16.

Najafov A, Mookhtiar AK, Luu HS et al (2019) TAM Kinases Promote Necroptosis by Regulating Oligomerization of MLKL. Mol Cell 75:457-468.e4. https://doi.org/10.1186/s12964-016-0142-1CrossRefPubMed

Title: Polyphyllin D induces necroptosis in neuroblastoma cells (IMR-32 and LA-N-2) in mice
Authors: Shunsuke Watanabe
Mikihiro Inoue
Tatsuya Suzuki
Yasuhiro Kondo
Mika Murayama
Publication date: 01-12-2023
Publisher: Springer Berlin Heidelberg
Keywords: Neuroblastoma
Neuroblastoma
Published in: Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-023-05425-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Polyphyllin D induces necroptosis in neuroblastoma cells (IMR-32 and LA-N-2) in mice

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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