Formoxanthone C,isolated from Cratoxylum formosum ssp. pruniflorum, reverses anticancer drug resistance by inducing both apoptosis and autophagy in human A549 lung cancer cells |
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Authors: | Chutima Kaewpiboon Nawong Boonnak Sirichat Kaowinn Young-Hwa Chung |
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Affiliation: | 1. Department of Biology, Faculty of Science, Thaksin University, Phatthalung 93210, Thailand;2. Department of Basic Science and Mathematics, Faculty of Science, Thaksin University, Songkhla 90000, Thailand;3. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea |
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Abstract: | Multidrug resistance (MDR) cancer toward cancer chemotherapy is one of the obstacles in cancer therapy. Therefore, it is of interested to use formoxanthone C (1,3,5,6-tetraoxygenated xanthone; XanX), a natural compound, which showed cytotoxicity against MDR human A549 lung cancer (A549RT-eto). The treatment with XanX induced not only apoptosis- in A549RT-eto cells, but also autophagy-cell death. Inhibition of apoptosis did not block XanX-induced autophagy in A549RT-eto cells. Furthermore, suppression of autophagy by beclin-1 small interfering RNAs (siRNAs) did not interrupt XanX-induced apoptosis, indicating that XanX can separately induce apoptosis and autophagy. Of interest, XanX treatment reduced levels of histone deacetylase 4 (HDAC4) protein overexpressed in A549RT-etocells. The co-treatment with XanX and HDAC4 siRNA accelerated both autophagy and apoptosis more than that by XanX treatment alone, suggesting survival of HDAC4 in A549RT-eto cells. XanX reverses etoposide resistance in A549RT-eto cells by induction of both autophagy and apoptosis, and confers cytotoxicity through down-regulation of HDAC4. |
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Keywords: | MDR cancer Formoxanthone C Apoptosis Autophagy HDAC4 |
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