Curcumin Analog Pentagamavunon-1 (PGV-1) Sensitizes Widr Cells to 5-Fluorouracil through Inhibition of NF-κB Activation

Document Type : Research Articles

Authors

1 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jalan Sekip Utara Yogyakarta, Indonesia.

2 Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI), Indonesia.

3 Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Japan.

Abstract

 
Cell cycle regulation and the NF-κB pathway in cancer cells are important in mediating resistance to 5-Fluorouracil (5-FU). Pentagamavunon-1 (PGV-1), a curcumin analog, is known to exhibit stronger growth inhibitory effects than curcumin itself in several cancer cells. In this study, we evaluated the potency of PGV-1 in combination with 5-FU in WiDr colon cancer cells. In MTT assays, PGV-1 did not only exhibit stronger growth inhibitory effects than both 5-FU and curcumin, but also enhanced the cytotoxicity of 5-FU. Flow cytometry demonstrated that single treatments with PGV-1 and 5-FU resulted in different effects on cell cycle profiles. PGV-1 induced G2/M arrest while 5-FU caused S-phase arrest at low concentration (1 μM) and G1-phase arrest at high concentration (100 μM). Interestingly, the combination of 5-FU and PGV-1 enhanced cell accumulation in S-phase. Although a single treatment with either 5-FU or PGV-1 increased cyclin D1 at the protein level, the combination treatment resulted in significant suppression. In addition, PGV-1 inhibited activation of NF-κB and suppressed the expression of cyclooxygenase-2, an NF-κB downstream protein. In conclusion, PGV-1 increased the cytotoxic effect of 5-FU on WiDr cells through inhibition of NF-κB activation.

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Asian Pacific Journal of Cancer Prevention
Volume 19, Issue 1
January 2018
Pages 49-56

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History

  • Receive Date: 05 May 2017
  • Revise Date: 13 June 2017
  • Accept Date: 18 December 2017

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