Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells

Berna Yıldırım; Melike Seçilmiş; Burcu Biltekin; Mete Hakan Karalök; Turgay Barut; Ayhan Bilir

doi:10.62425/rtpharma.1854497

Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells

Abstract

Objective: To investigate whether pharmacological agents associated with autophagy induction or inhibition modulate vinorelbine-induced cytotoxic responses in SH-SY5Y neuroblastoma cells. Methods: SH-SY5Y neuroblastoma cells were treated with vinorelbine, lithium chloride (LiCl), medroxyprogesterone acetate (MPA), or clomipramine, either individually or in combination. Cell viability was assessed using the Trypan Blue exclusion assay in a dose- and time-dependent manner. Treatment-induced ultrastructural alterations were examined by transmission electron microscopy after 96 hours. Results: All agents reduced cell viability in a dose- and time-dependent manner. LiCl and clomipramine produced rapid loss of viability, whereas vinorelbine and MPA caused more gradual reductions. Combination treatments, particularly vinorelbine combined with LiCl or clomipramine, resulted in markedly enhanced cytotoxic effects, reducing cell viability to below 20% at 96 hours. Ultrastructural analysis revealed distinct stress-associated morphologies: vinorelbine induced mitotic stress accompanied by secondary autophagic vacuole formation; LiCl caused extensive cytoplasmic vacuolization consistent with enhanced autophagy-associated stress; clomipramine led to pronounced vacuolation and cytoplasmic disorganization; and MPA induced mixed autophagy- and apoptosis-associated features. Combination treatments further intensified these ultrastructural alterations. Although ultrastructural data were not available for the vinorelbine plus MPA group, viability data and single-agent profiles suggest overlapping cytostatic and autophagy-associated stress responses. Conclusion: These findings indicate that agents associated with autophagy induction or inhibition can substantially influence vinorelbine-induced cytotoxic responses in SH-SY5Y neuroblastoma cells. Modulation of autophagy-related stress pathways may represent a rational strategy to enhance the cytotoxic efficacy of microtubule-disrupting agents in neuroblastoma models.

Keywords

References

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Details

Primary Language

English

Subjects

Cancer Therapy (Excl. Chemotherapy and Radiation Therapy), Oncology and Carcinogenesis (Other)

Journal Section

Research Article

Authors

Berna Yıldırım
0000-0002-4479-2586
Türkiye

Melike Seçilmiş
0000-0002-0749-1821
Türkiye

Burcu Biltekin
0000-0002-8435-6797
Türkiye

Mete Hakan Karalök
0000-0002-6814-6212
Türkiye

Turgay Barut
0000-0001-5915-9292
United States

Ayhan Bilir ^*
0009-0009-9399-5927
Türkiye

Early Pub Date

February 20, 2026

Publication Date

February 20, 2026

Submission Date

January 2, 2026

Acceptance Date

February 19, 2026

Published in Issue

Year 2026 Volume: 4 Number: 1

DOI

https://doi.org/10.62425/rtpharma.1854497

IZ

https://izlik.org/JA99AX57UX

Cite

RIS / Bibtex

APA

Yıldırım, B., Seçilmiş, M., Biltekin, B., Karalök, M. H., Barut, T., & Bilir, A. (2026). Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells. Recent Trends in Pharmacology, 4(1), 8-17. https://doi.org/10.62425/rtpharma.1854497

AMA

1.Yıldırım B, Seçilmiş M, Biltekin B, Karalök MH, Barut T, Bilir A. Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells. Recent Trends in Pharmacology. 2026;4(1):8-17. doi:10.62425/rtpharma.1854497

Chicago

Yıldırım, Berna, Melike Seçilmiş, Burcu Biltekin, Mete Hakan Karalök, Turgay Barut, and Ayhan Bilir. 2026. “Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells”. Recent Trends in Pharmacology 4 (1): 8-17. https://doi.org/10.62425/rtpharma.1854497.

EndNote

Yıldırım B, Seçilmiş M, Biltekin B, Karalök MH, Barut T, Bilir A (April 1, 2026) Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells. Recent Trends in Pharmacology 4 1 8–17.

IEEE

[1]B. Yıldırım, M. Seçilmiş, B. Biltekin, M. H. Karalök, T. Barut, and A. Bilir, “Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells”, Recent Trends in Pharmacology, vol. 4, no. 1, pp. 8–17, Apr. 2026, doi: 10.62425/rtpharma.1854497.

ISNAD

Yıldırım, Berna - Seçilmiş, Melike - Biltekin, Burcu - Karalök, Mete Hakan - Barut, Turgay - Bilir, Ayhan. “Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells”. Recent Trends in Pharmacology 4/1 (April 1, 2026): 8-17. https://doi.org/10.62425/rtpharma.1854497.

JAMA

1.Yıldırım B, Seçilmiş M, Biltekin B, Karalök MH, Barut T, Bilir A. Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells. Recent Trends in Pharmacology. 2026;4:8–17.

MLA

Yıldırım, Berna, et al. “Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells”. Recent Trends in Pharmacology, vol. 4, no. 1, Apr. 2026, pp. 8-17, doi:10.62425/rtpharma.1854497.

Vancouver

1.Berna Yıldırım, Melike Seçilmiş, Burcu Biltekin, Mete Hakan Karalök, Turgay Barut, Ayhan Bilir. Vinorelbine- Autophagy Agent Combinations Induce Synergistic Cytotoxicity in SH-SY5Y Neuroblastoma Cells. Recent Trends in Pharmacology. 2026 Apr. 1;4(1):8-17. doi:10.62425/rtpharma.1854497