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Mol Med Rep. 2017 Dec;16(6):9715-9720. doi: 10.3892/mmr.2017.7815. Epub 2017 Oct 17.

Autophagy is essential for flavopiridol‑induced cytotoxicity against MCF‑7 breast cancer cells.

Author information

1
Nephrology Department, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China.
2
Nuclear Medicine Department, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China.
3
Nuclear Medicine Department, Qilu Hospital, Jinan, Shandong 250012, P.R. China.

Abstract

Flavopiridol (FP) exerts antitumoral effects by triggering tumor cell cycle arrest and cytotoxicity in human breast cancer cell lines. The potent antitumor activity of FP is through its inhibition of cyclin‑dependent kinases; however, this may not be the only mechanism of action. The present study aimed to investigate whether FP is able to induce autophagy and to examine the effects of autophagy on cell death in FP‑treated MCF‑7 human breast cancer cells. MCF‑7 cells were treated with either FP alone or FP in combination with chloroquine (CQ). Expression levels of autophagy‑related protein LC3B‑II and p62/sequestosome 1 (SQSTM1) were used to monitor autophagic flux. MCF‑7 cells were transfected with autophagy‑related 5 (ATG5) small interfering (si)RNA to block autophagy. Cell viability and cell cycle status were determined. Following incubation with FP, MCF‑7 cells exhibited significantly higher autophagy compared with untreated control cells, and the level of autophagy is comparable with cells under rapamycin induction, which was verified by immunodetection of LC3B‑II and p62/SQSTM1 expression and inhibition by CQ. The addition of CQ treatment or ATG5‑siRNA transfection against autophagy components attenuated the cytotoxic effects of FP treatment of MCF‑7 cells. Furthermore, this autophagy inhibition did not impair the FP‑induced cell cycle arrest. These results revealed that autophagy may be involved in FP‑induced MCF‑7 cell death and autophagy inhibition enhanced the tumor cell pro‑survival ability. It is possibly that potential autophagy regulatory drugs may be used as a chemotherapy adjuvant.

PMID:
29039550
DOI:
10.3892/mmr.2017.7815
[Indexed for MEDLINE]

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