Involvement of mitochondria and caspase pathways in n-demethyl-clarithromycin-induced apoptosis in human cervical cancer hela cell

ABSTRACT AIM: To study the mechanisms by which _N_-demethyl-clarithromycin (NDC) induces human cervical cancer HeLa cell apoptosis _in vitro_. METHODS: The viability of

_N_-demethyl-clarithromycin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation

was assayed by agarose gel electrophoresis. Measurement of mitochondrial transmembrane potential was analyzed by a FACScan flowcytometer. Caspase-3, poly-(ADP-ribose) polymerase (PARP),

caspase-activated DNase (ICAD), Bcl-2, Bax, p53, and SIRT1 protein expression and the release of cytochrome c were detected by Western blot analysis. RESULTS: _N_-demethyl-clarithromycin, an

anti-inflammatory substance, inhibited HeLa cell growth in a dose- and time-dependent manner. _N_-demethyl-clarithromycin induced HeLa cell death through the apoptotic pathways. The

pancaspase inhibitor (z-VAD-fmk), caspase-3 inhibitor (z-DEVD-fmk) andthecaspase-9 inhibitor (z-LEHD-fmk) partially enhanced cell viability induced by _N_-demethyl-clarithromycin, but the

caspase-8 inhibitor (z-IETD-fmk) had almost no effect. Caspase-3 was activated then followed by the degradation of caspase-3 substrates, the inhibitor of ICAD and PARP. Simultaneously,

mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c in the cytosol was increased. _N_-demethyl-clarithromycin upregulated the expression ratio of

mitochondrial Bax/Bcl-2, and significantly increased the expression of the p53 protein. It also downregulated anti-apoptotic protein SIRT1 expression. CONCLUSION: _N_-demethyl-clarithromycin

induced apoptosis in HeLa cells via the mitochondrial pathway. SIMILAR CONTENT BEING VIEWED BY OTHERS APOPTOTIC EFFECT OF NOVEL PYRAZOLONE-BASED DERIVATIVE [CU(PMPP-SAL)(ETOH)] ON HELA

CELLS AND ITS MECHANISM Article Open access 26 October 2020 PYRAZOLE DERIVATIVES OF PYRIDINE AND NAPHTHYRIDINE AS PROAPOPTOTIC AGENTS IN CERVICAL AND BREAST CANCER CELLS Article Open access

01 April 2023 _METASEQUOIA GLYPTOSTROBOIDES_ POTENTIATES ANTICANCER EFFECT AGAINST CERVICAL CANCER VIA INTRINSIC APOPTOSIS PATHWAY Article Open access 13 January 2021 ARTICLE PDF REFERENCES

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Pharmaceutical University, Shenyang, 110016, China Ai-min Qiao & Ying-liang Wu * China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University,

Shenyang, 110016, China Ai-min Qiao & Takashi Ikejima * Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan Shin-ichi Tashiro & 

Satoshi Onodera * School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China Wei-ge Zhang Authors * Ai-min Qiao View author publications You can also

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CORRESPONDING AUTHOR Correspondence to Ying-liang Wu. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Qiao, Am., Ikejima, T., Tashiro, Si. _et al._

Involvement of mitochondria and caspase pathways in _N_-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell. _Acta Pharmacol Sin_ 27, 1622–1629 (2006).

https://doi.org/10.1111/j.1745-7254.2006.00444.x Download citation * Received: 30 April 2006 * Accepted: 11 July 2006 * Issue Date: 01 December 2006 * DOI:

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not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _N_-demethyl-clarithromycin * HeLa cells * caspase

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