Cancer Research and Treatment

Sabarish Ramachandran

1 Article

Augmentation of Sodium Butyrate-induced Apoptosis by Phosphatidylinositol 3-kinase Inhibition in the Human Cervical Cancer Cell-line: Jung Kyu Park, Chi Heum Cho, Sabarish Ramachandran, So Jin Shin, Sang Hoon Kwon, Sun Young Kwon, Soon Do Cha; Cancer Res Treat. 2006;38(2):112-117. Published online April 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.2.112

Purpose

Sodium butyrate (NaBT) is principally a histone deacetylase (HDAC) inhibitor, and it has the potential to arrest HPV-positive carcinoma cells at the G1 to S phase transition of the cell cycle. The aim of study was to determine whether phosphatidylinositol 3-kinase (PI3K) inhibition can enhance the inhibitory effect of NaBT on a human cervical cancer cell line (HeLa).

Materials and Methods

Cervical cancer cells (HeLa) were treated with NaBT alone or in combination with the PI3K inhibitors wortmannin or LY294002. Cell viability analysis and FACS analysis were carried out. The expressions of the cell cycle related proteins were evaluated by Western-blot analysis.

Results

Inhibition of PI3K enhanced NaBT-mediated apoptosis and this decreased the HeLa cell viability. Either wortmannin or LY294002, combined with NaBT, enhanced the activation of caspase 3 and caspase 9, and this enhanced the subsequent cleavage of poly (ADP-ribose) polymerase (PARP). Cervical cancer cells were arrested in the subG1 and G2/M phase, as was detected by FACS analysis. NaBT treatment in combination with PI3K inhibitors showed the increased expression of the CDK inhibitors p21^Cip1/Waf1 and p27^Kip1, in a p53 dependent manner, and also the increased dephosphorylation of Rb whereas there was a reduction in the expression levels of cyclin A, cyclin D1 and cyclin B1.

Conclusion

The results demonstrate that inhibition of PI3K enhances NaBT-mediated cervical cancer cell apoptosis through the activation of the caspase pathway. Moreover, these findings will support future investigation using the PI3K inhibitors in combination with adjuvant treatment for treating carcinoma of the cervix.

Citations

Citations to this article as recorded by

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Tingting Wang, Weili Li, Mingya Cai, Shushen Ji, Yufang Wang, Nan Huang, Yancheng Jiang, Zhishan Zhang, Jack A. Gilbert
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Cancers.2023; 15(8): 2222. CrossRef
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Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
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Molecular Biology of the Cell.2020; 31(26): 2904. CrossRef
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Omana P. Mathew, Kasturi Ranganna, Joseph Mathew, Meiling Zhu, Zivar Yousefipour, Chelliah Selvam, Shirlette G. Milton
International Journal of Molecular Sciences.2019; 20(12): 2902. CrossRef
The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy
Afsane Bahrami, Malihe Hasanzadeh, Seyed Mahdi Hassanian, Soodabeh ShahidSales, Majid Ghayour‐Mobarhan, Gordon A. Ferns, Amir Avan
Journal of Cellular Biochemistry.2017; 118(12): 4163. CrossRef
The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways
Igor Hrgovic, Monika Doll, Johannes Kleemann, Xiao-Fan Wang, Nadja Zoeller, Andreas Pinter, Stefan Kippenberger, Roland Kaufmann, Markus Meissner
BMC Cancer.2016;[Epub] CrossRef
The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses
Lifang Zhang, Jianhong Wu, Ming Tat Ling, Liang Zhao, Kong-Nan Zhao
Molecular Cancer.2015;[Epub] CrossRef
Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells
Elzbieta Pastwa, Tomasz Poplawski, Urszula Lewandowska, Stella B. Somiari, Janusz Blasiak, Richard I. Somiari
The International Journal of Biochemistry & Cell Biology.2014; 53: 423. CrossRef
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Archives of Medical Research.2014; 45(7): 525. CrossRef
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TAKESHI YAMADA, MANO HORINAKA, MASAHIDE SHINNOH, TAKASHI YOSHIOKA, TSUNEHARU MIKI, TOSHIYUKI SAKAI
International Journal of Oncology.2013; 43(4): 1080. CrossRef
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Andrew J. Vincent, Suping Ren, Lillianne G. Harris, Daniel J. Devine, Rajeev S. Samant, Oystein Fodstad, Lalita A. Shevde
FEBS Letters.2012; 586(19): 3429. CrossRef
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Agnieszka Anna Rawłuszko, Sylwia Sławek, Armin Gollogly, Katarzyna Szkudelska, Paweł Piotr Jagodziński
Biomedicine & Pharmacotherapy.2012; 66(2): 77. CrossRef
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Liying Yang, Tomohisa Horibe, Masayuki Kohno, Mari Haramoto, Koji Ohara, Raj K. Puri, Koji Kawakami
Molecular Cancer Therapeutics.2012; 11(1): 235. CrossRef
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Molecular Pharmaceutics.2009; 6(2): 513. CrossRef

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