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Alterations of MicroRNA Expression Patterns in Human Cervical Carcinoma Cells (Ca Ski) toward 1′S-1′-Acetoxychavicol Acetate and Cisplatin

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Abstract

The aims of this study were to investigate the combined effects of a natural compound 1′S-1′-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski—low cisplatin sensitivity and HeLa—high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.

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Authors and Affiliations

  1. Institute of Biological Science (Genetics & Molecular Biology), Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Neoh Hun Phuah MSc, Lionel LA In PhD & Noor Hasima Nagoor PhD

  2. Department of Chemistry, Centre for Natural Product Research and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia

    Mohamad Nurul Azmi MSc & Khalijah Awang PhD

  3. Institute of Biological Science (Ecology and Biodiversity), Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia

    Halijah Ibrahim PhD

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  1. Neoh Hun Phuah MSc
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  2. Lionel LA In PhD
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  3. Mohamad Nurul Azmi MSc
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  4. Halijah Ibrahim PhD
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  6. Noor Hasima Nagoor PhD
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Correspondence to Noor Hasima Nagoor PhD.

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Phuah, N.H., In, L.L., Azmi, M.N. et al. Alterations of MicroRNA Expression Patterns in Human Cervical Carcinoma Cells (Ca Ski) toward 1′S-1′-Acetoxychavicol Acetate and Cisplatin. Reprod. Sci. 20, 567–578 (2013). https://doi.org/10.1177/1933719112459220

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