2. Academic Validation
  3. Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence

Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence

  • Sci Rep. 2019 Oct 16;9(1):14867. doi: 10.1038/s41598-019-51244-3.
Beni Lestari 1,  Ikuko Nakamae 1,  Noriko Yoneda-Kato 1,  Tsumoru Morimoto 2,  Shigehiko Kanaya 3,  Takashi Yokoyama 1,  Masafumi Shionyu 4,  Tsuyoshi Shirai 4,  Edy Meiyanto 5,  Jun-Ya Kato 6
Affiliations

Affiliations

  • 1 Laboratory of Tumor Cell Biology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
  • 2 Laboratory of Synthetic Organic Chemistry, Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
  • 3 Laboratory of Computational Systems Biology, Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
  • 4 Nagahama Institute of Bio-Science and Technology, Nagahama, Japan.
  • 5 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
  • 6 Laboratory of Tumor Cell Biology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan. jkata@bs.naist.jp.
PMID: 31619723 DOI: 10.1038/s41598-019-51244-3
Abstract

We previously showed that curcumin, a phytopolyphenol found in turmeric (Curcuma longa), targets a series of Enzymes in the ROS metabolic pathway, induces irreversible growth arrest, and causes Apoptosis. In this study, we tested Pentagamavunon-1 (PGV-1), a molecule related to curcumin, for its inhibitory activity on tumor cells in vitro and in vivo. PGV-1 exhibited 60 times lower GI50 compared to that of curcumin in K562 cells, and inhibited the proliferation of cell lines derived from leukemia, breast adenocarcinoma, cervical Cancer, uterine Cancer, and pancreatic Cancer. The inhibition of growth by PGV-1 remained after its removal from the medium, which suggests that PGV-1 irreversibly prevents proliferation. PGV-1 specifically induced prometaphase arrest in the M phase of the cell cycle, and efficiently induced cell senescence and cell death by increasing intracellular ROS levels through inhibition of ROS-metabolic Enzymes. In a xenograft mouse model, PGV-1 had marked anti-tumor activity with little side effects by oral administration, whereas curcumin rarely inhibited tumor formation by this administration. Therefore, PGV-1 is a potential therapeutic to induce tumor cell Apoptosis with few side effects and low risk of relapse.

Figures
Products