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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제28권 제4호
- 발행연도
- 2018.1
- 수록면
- 542 - 550 (9page)
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Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88- 1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to G2/M cell cycle arrest. Further studies also showed that WK- 88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and ER-α in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.
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참고문헌 (29)
참고문헌 신청
Siegel RL / 2016 / Cancer statistics / CA Cancer J. Clin. 66:7~30
Gonzalez-Angulo AM / 2007 / Overview of resistance to systemic therapy in patients with breast cancer / Adv. Exp. Med. Biol. 608:1~22
Schopf FH / 2017 / The Hsp90 chaperone machinery / Nat. Rev. Mol. Cell Biol. 18:345~360
Sankhala KK / 2011 / Heat shock proteins: a potential anticancer target / Curr. Drug Targets 12:2001~2008
Sausville EA / 2003 / Clinical development of 17-allylamino, 17-demethoxygeldanamycin / Curr. Cancer Drug Targets 3:377~383
Gonzalez-Angulo AM / 2007 / Overview of resistance to systemic therapy in patients with breast cancer / Adv. Exp. Med. Biol. 608:1~22
Schopf FH / 2017 / The Hsp90 chaperone machinery / Nat. Rev. Mol. Cell Biol. 18:345~360
Sankhala KK / 2011 / Heat shock proteins: a potential anticancer target / Curr. Drug Targets 12:2001~2008
Sausville EA / 2003 / Clinical development of 17-allylamino, 17-demethoxygeldanamycin / Curr. Cancer Drug Targets 3:377~383
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