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Zoledronic acid induces apoptosis and autophagy in cervical cancer cells

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Tumor Biology

Abstract

Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan

    I-Te Wang

  2. Department of Family Medicine, Taipei Medical University—Shuang Ho Hospital, New Taipei, Taiwan

    Shou-Chu Chou & Ying-Chin Lin

  3. Department of Occupational Medicine, Taipei Medical University—Shuang Ho Hospital, New Taipei, Taiwan

    Shou-Chu Chou & Ying-Chin Lin

  4. Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu Hsing Street, 110, Taipei, Taiwan

    Ying-Chin Lin

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  1. I-Te Wang
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Correspondence to Ying-Chin Lin.

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Wang, IT., Chou, SC. & Lin, YC. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells. Tumor Biol. 35, 11913–11920 (2014). https://doi.org/10.1007/s13277-014-2460-5

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  • DOI: https://doi.org/10.1007/s13277-014-2460-5

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