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Doxorubicin-induced mitophagy contributes to drug resistance in cancer stem cells from HCT8 human colorectal cancer cells
- Source :
- Cancer letters. 388
- Publication Year :
- 2016
-
Abstract
- Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133+/CD44+ CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs. Interestingly, the level of mitochondrial superoxide was detected to be significantly lower in CSCs than in parental cells after DXR treatment. Furthermore, the mitophagy level and expression of BNIP3L, a mitophagy regulator, were significantly higher in CSCs than in parental cells after DXR treatment. Silencing BNIP3L significantly halted mitophagy and enhanced the sensitivity to DXR in CSCs. Our data suggested that mitophagy, but not non-selective autophagy, likely contributes to drug resistance in CSCs isolated from HCT8 cells. Further studies in other cancer cell lines will be needed to confirm our findings.
- Subjects :
- 0301 basic medicine
Cancer Research
PINK1
Biology
Transfection
03 medical and health sciences
0302 clinical medicine
Cancer stem cell
Cell Line, Tumor
Mitophagy
medicine
Gene silencing
Humans
Doxorubicin
FADD
Antibiotics, Antineoplastic
CD44
Autophagy
Cell biology
030104 developmental biology
Oncology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
biology.protein
Neoplastic Stem Cells
Colorectal Neoplasms
medicine.drug
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 388
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....800570e85fd6ed683bf3f1d3ea097a39