Commitment toward cell death by activation of autophagy with survivin inhibitor YM155 in two canine squamous cell carcinoma cell lines with high expression of survivin
| Autor: | Tomoyo Ikeda, Hono Saima, Makoto Bonkobara, Ryo Miyamoto, Hiroyuki Tani, Kyoichi Tamura |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Poly ADP ribose polymerase Survivin Antineoplastic Agents Apoptosis Immunoglobulin light chain Cleavage (embryo) Inhibitor of Apoptosis Proteins Dogs Cell Line Tumor Autophagy Biomarkers Tumor Cytotoxic T cell Animals Humans Amebicides Dog Diseases General Veterinary Cell Death Chemistry Imidazoles Chloroquine Gene Expression Regulation Neoplastic Cell culture Cancer research Carcinoma Squamous Cell Naphthoquinones |
| Zdroj: | Research in veterinary science. 135 |
| ISSN: | 1532-2661 |
| Popis: | Canine squamous cell carcinoma (SCC) is difficult to treat if local therapy is not feasible. Recently, survivin inhibitor YM155 was shown to have growth inhibitory activity on high-survivin-expressing canine SCC cell lines HAPPY and SQ4. Here, the mechanisms underlying the effect of YM155 on these cell lines were investigated. YM155 induced cleavage of poly(ADP-ribose) polymerase (PARP) in HAPPY, but not in SQ4 cells. Analyzing two autophagy markers, the level of microtubule-associated protein 1 light chain 3 (LC3)-II and the LC3-II/LC3-I ratio, indicated that YM155 activates autophagy in both cell lines, and this activation occurs prior to PARP cleavage in HAPPY cells. Moreover, inhibition of autophagic flux by chloroquine almost completely prevented the toxic effect of YM155 in both cell lines. Although there are differences in their eventual cell death type, both cell lines may be committed to cell death by activation of autophagy with YM155. Activation of autophagy is likely to be a key mechanism in the growth-inhibitory effects of YM155 in these lines. These data provide new insights into the cytotoxic mechanism of YM155 in canine SCC cells. |
| Databáze: | OpenAIRE |
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