Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2012

Open Access 01-12-2012 | Primary research

Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel

Authors: Anthony Stanislaus, Athirah Bakhtiar, Diyana Salleh, Snigdha Tiash, Tahereh Fatemian, Sharif Hossain, Toshihiro Akaike, Ezharul Hoque Chowdhury

Published in: Cancer Cell International | Issue 1/2012

Login to get access

Abstract

Background

RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression.

Results

Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs.

Conclusion

Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.
Appendix
Available only for authorised users
Literature
1.
de Fougerolles AR: Delivery vehicles for small interfering RNA in vivo. Hum Gene Ther. 2008, 19: 125-132. 10.1089/hum.2008.928.CrossRefPubMed
2.
3.
Lee NS, Rossi JJ: Control of HIV-1 replication by RNA interference. Virus Res. 2004, 102: 53-58. 10.1016/j.virusres.2004.01.015.CrossRefPubMed
4.
Grünweller A, Hartmann RK: RNA interference as a gene-specific approach for molecular medicine. Curr Med Chem. 2005, 12: 3143-3161. 10.2174/092986705774933489.CrossRefPubMed
5.
Ito M, Kawano K, Miyagishi M, Taira K: Genome-wide application of RNAi to the discovery of potential drug targets. FEBS Lett. 2005, 579: 5988-5995. 10.1016/j.febslet.2005.08.015.CrossRefPubMed
6.
Lu PY, Xie F, Woodle MC: In vivo application of RNA interference: from functional genomics to therapeutics. Adv Genet. 2005, 54: 117-142.PubMed
7.
Chowdhury EH: Nuclear targeting of viral and non-viral DNA. Expert Opin Drug Deliv. 2009, 6: 697-703. 10.1517/17425240903025744.CrossRefPubMed
8.
Chowdhury EH: Strategies for tumor-directed delivery of siRNA. Expert Opin Drug Deliv. 2011, 8: 389-401. 10.1517/17425247.2011.554817.CrossRefPubMed
9.
Reischl D, Zimmer A: Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomedicine. 2009, 5: 8-20. 10.1016/j.nano.2008.06.001.CrossRefPubMed
10.
Ryther RC, Flynt AS, Phillips JA, Patton JG: siRNA therapeutics: big potential from small RNAs. Gene Ther. 2005, 12: 5-11. 10.1038/sj.gt.3302356.CrossRefPubMed
11.
van de Water FM, Boerman OC, Wouterse AC, Peters JG, Russel FG, Masereeuw R: Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug Metab Dispos. 2006, 34: 1393-1397. 10.1124/dmd.106.009555.CrossRefPubMed
12.
Dickerson EB, Blackburn WH, Smith MH, Kapa LB, Lyon LA, McDonald JF: Chemosensitization of cancer cells by siRNA using targeted nanogel delivery. BMC Cancer. 2010, 10: 1-11. 10.1186/1471-2407-10-1.CrossRef
13.
Roberts PJ, Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 2007, 26: 3291-3310. 10.1038/sj.onc.1210422.CrossRefPubMed
14.
Brader S, Eccles SA: Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori. 2004, 90: 2-8.PubMed
15.
Kahl CR, Means AR: Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev. 2003, 24: 719-6. 10.1210/er.2003-0008.CrossRefPubMed
16.
17.
Colomer J, Means AR: Physiological roles of the Ca2+/CaM-dependent protein kinase cascade in health and disease. Subcell Biochem. 2007, 45: 169-214. 10.1007/978-1-4020-6191-2_7.CrossRefPubMed
18.
Hossain S, Stanislaus A, Chua MJ, Tada S, Tagawa Y, Chowdhury EH, Akaike T: Carbonate apatite-facilitated intracellularly delivered siRNA for efficient knockdown of functional genes. J Control Release. 2010, 147: 101-108. 10.1016/j.jconrel.2010.06.024.CrossRefPubMed
19.
Stanislaus A, Hossain S, Chua MJ, Kunnath AP, Wen QC, Syakira SN, Siong GY, Loong SW, Othman I, Akaike T, Chowdhury EH: Fabrication and intracellular delivery of siRNA/carbonate apatite nano-composites for effective knockdown of cyclin B1 gene. Drugs Therp Studies. 2011, 1: 26-30.
20.
Cowell CF, Döppler H, Yan IK, Hausser A, Umezawa Y, Storz P: Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signalling. J Cell Sci. 2009, 122: 919-8. 10.1242/jcs.041061.PubMedCentralCrossRefPubMed
21.
Kim M, Jung J, Lee K: Roles of ERK, PI3 kinase, and PLC-γ pathways induced by overexpression of translationally controlled tumor protein in HeLa cells. Arch Biochem Biophys. 2009, 485: 82-87. 10.1016/j.abb.2009.02.002.CrossRefPubMed
22.
Li CJ, Heim R, Lu P, Pu Y, Tsien RY, Chang DC: Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique. J Cell Sci. 1999, 112: 1567-1577.PubMed
23.
Jang MK, Goo YH, Sohn YC, Kim YS, Lee SK, Kang H, Cheong J, Lee JW: Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit. J Biol Chem. 2001, 276: 20005-20010. 10.1074/jbc.M010211200.CrossRefPubMed
24.
Eastman A: Activation of programmed cell death by anticancer agents: cisplatin as a model system. Cancer Cell. 1990, 2: 275-279.
25.
Alberts DS, Garcia D, Mason-Liddil N: Cisplatin in advanced cancer of the cervix: an update. Semin Oncol. 1991, 18: 11-24.PubMed
26.
Nishio K, Sugimoto Y, Fujiwara Y, Ohmori T, Morikage T, Takeda Y, Ohata M, Saijo N: Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by cis-diamminedichloroplatinum(II). J Clin Invest. 1992, 89: 1622-1628. 10.1172/JCI115758.PubMedCentralCrossRefPubMed
27.
Kristensen G, Tropé C: Endometrial cancer: the management of high-risk disease. Curr Oncol Rep. 2004, 6: 471-475. 10.1007/s11912-004-0078-2.CrossRefPubMed
28.
Nguyen HN, Nordqvist SR: Chemotherapy of advanced and recurrent cervical carcinoma. Semin Surg Oncol. 1999, 16: 247-250. 10.1002/(SICI)1098-2388(199904/05)16:3<247::AID-SSU10>3.0.CO;2-4.CrossRefPubMed
29.
Thompson MG, Hickman JA: Doxorubicin interactions at the membrane: evidence for a biphasic modulation of inositol lipid metabolism. Eur J Cancer. 1991, 27: 1263-1268. 10.1016/0277-5379(91)90094-T.CrossRefPubMed
30.
De Vincenzo R, Amadio G, Ricci C, Licameli A, Ferrandina G, Capelli G, Scambia G: Treatment of cervical cancer in Italy: strategies and their impact on the women. Vaccine. 2009, 27: A39-A45.CrossRefPubMed
31.
Pectasides D, Kamposioras K, Papaxoinis G, Pectasides E: Chemotherapy for recurrent cervical cancer. Cancer Treat Rev. 2008, 34: 603-613. 10.1016/j.ctrv.2008.05.006.CrossRefPubMed
32.
Melander Gradin H, Marklund U, Larsson N, Chatila TA, Gullberg M: Regulation of microtubule dynamics by Ca2+/Calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18. Mol Cell Biol. 1997, 17: 3459-3467.PubMedCentralCrossRefPubMed
33.
Gallagher BM: Microtubule-stabilizing natural products as promising cancer therapeutics. Curr Med Chem. 2007, 14: 2959-2967. 10.2174/092986707782794014.CrossRefPubMed
Metadata
Title
Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
Authors
Anthony Stanislaus
Athirah Bakhtiar
Diyana Salleh
Snigdha Tiash
Tahereh Fatemian
Sharif Hossain
Toshihiro Akaike
Ezharul Hoque Chowdhury
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2012
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-12-30

Other articles of this Issue 1/2012

Cancer Cell International 1/2012 Go to the issue

Primary research

2-Methoxyestradiol-bis-sulphamate refrains from inducing apoptosis and autophagy in a non-tumorigenic breast cell line

Primary research

Knock-down of Kaiso induces proliferation and blocks granulocytic differentiation in blast crisis of chronic myeloid leukemia

Primary research

Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

Primary research

Mutations increased overexpression of Notch 1 in T-cell acute lymphoblastic leukemia

Primary research

Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells

Primary research

Analysis of volatile organic compounds released from human lung cancer cells and from the urine of tumor-bearing mice
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits