Open Access iconOpen Access

ARTICLE

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

XIAOQI WU1,2,#, YECHUAN HE1,2,#, YEQIN YUAN4, XIAN TAN1,2, LIN ZHU1,2, DANLING WANG1,2,4, BINYUAN JIANG3,4,*

1 Hengyang Medical School, University of South China, Hengyang, 421001, China
2 Institute for Future Sciences, University of South China, Changsha, 410008, China
3 Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, China
4 Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, China

* Corresponding Author: BINYUAN JIANG. Email: email
# Equal contribution

(This article belongs to the Special Issue: Navigating the Interplay of Cancer, Autophagy, ER Stress, Cell Cycle and Apoptosis: Mechanisms, Therapies, and Future Directions)

BIOCELL 2024, 48(5), 861-872. https://doi.org/10.32604/biocell.2024.048758

Abstract

Background: Nasopharyngeal carcinoma (NPC) exhibits a significant prevalence in the southern regions of China, and paclitaxel (PTX) is frequently employed as a medication for managing advanced NPC. However, drug resistance is typically accompanied by a poor prognosis. Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy. Methods: This study investigated whether 3-Methyladenine (3-MA) could potentiated the effect of PTX and its potential molecular mechanism. Samples were divided into the following categories: Negative control (NC) with the solvent dimethyl sulfoxide (DMSO, 0.5% v/v), PTX (400 nM), 3-MA (4 mM), and PTX (400 nM) + 3-MA (4 mM). The viability of NPC cells was assessed using both the cell counting kit-8 (CCK-8) assay and the colony formation assay. Microscopic observation was performed to identify morphological cell changes. Flow cytometry was used to assess cell cycle status, mitochondrial membrane potential (MMP), and apoptotic cells. Western blotting was conducted to quantify the protein expression. Results: 3-MA enhanced PTX-specific inhibition of NPC cell proliferation. PTX, either alone or in combination with 3-MA, caused cell cycle halt at the G/M phase in the majority of NPC cells, and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone. Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1 (CDK1), a key molecule in shifting cells from mitotic arrest to apoptosis, led to a reduction in Myeloid Cell Leukemia 1 (MCL-1) expression and an increase in Poly (ADP-ribose) polymerase (PARP) cleavage. Conclusion: The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Keywords


Cite This Article

APA Style
WU, X., HE, Y., YUAN, Y., TAN, X., ZHU, L. et al. (2024). 3-methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell. BIOCELL, 48(5), 861-872. https://doi.org/10.32604/biocell.2024.048758
Vancouver Style
WU X, HE Y, YUAN Y, TAN X, ZHU L, WANG D, et al. 3-methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell. BIOCELL . 2024;48(5):861-872 https://doi.org/10.32604/biocell.2024.048758
IEEE Style
X. WU et al., "3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell," BIOCELL , vol. 48, no. 5, pp. 861-872. 2024. https://doi.org/10.32604/biocell.2024.048758



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 343

    View

  • 143

    Download

  • 0

    Like

Share Link