Antineoplaston induces G1 arrest by PKCα and MAPK pathway in SKBR-3 breast cancer cells

  • Authors: Teruhiko Fujii, Anna M. Nakamura, Goro Yokoyama, Miki Yamaguchi, Kosuke Tayama, Keisuke Miwa, Uhi Toh, Daisuke Kawamura, Kazuo Shirouzu, Hideaki Yamana, Michihiko Kuwano, Hideaki Tsuda
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  • Published online on: Monday, August 1, 2005
  • Pages: 489-494
  • DOI: 10.3892/or.14.2.489

Abstract

Antineoplastons such as A10 include naturally occurring peptides and amino acid derivatives that control the neoplastic growth of cells. The mechanism underlying this antitumor effect was investigated using the breast cancer cell line, SKRB-3. Cells treated with A10 were monitored for any changes in cell cycle, expression of protein kinase C (PKC), or intracellular signal transduction, particularly phos-phorylation of mitogen-activated protein kinase (MAPK). The A10 markedly inhibited SKBR-3 proliferation due to arrest in the G1 phase. A10 down-regulated the expression of PKCα protein, resulting in inhibition of extracellular signal-regulated kinase (ERK) MAPK phosphorylation. This increased the expression of p16 and p21 protein, with resultant inhibition of Rb phosphorylation, leading to G1 arrest. This study has defined a pathway in which A10 arrested SKBR-3 cells in the G1 phase via PKCα and MAPK. Our findings indicate that the antineoplaston A10 antitumor effect could be utilized as an effective therapy for breast cancer patients.
Journal Cover

August 2005
Volume 14 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.191
Ranked #33/202 Oncology
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APA
Fujii, T., Nakamura, A., Yokoyama, G., Yamaguchi, M., Tayama, K., Miwa, K., Toh, U., Kawamura, D., Shirouzu, K., Yamana, H., Kuwano, M., & Tsuda, H. (2005). Antineoplaston induces G1 arrest by PKCα and MAPK pathway in SKBR-3 breast cancer cells. Oncology Reports, 14(2), 489-494.
MLA
Fujii, Nakamura, Yokoyama, Yamaguchi, Tayama, Miwa, Toh, Kawamura, Shirouzu, Yamana, Kuwano, and Hideaki Tsuda. "Antineoplaston induces G1 arrest by PKCα and MAPK pathway in SKBR-3 breast cancer cells." Oncology Reports Oncology Reports 14.2 (2005): 489-494.
Chicago
Fujii, Nakamura, Yokoyama, Yamaguchi, Tayama, Miwa, Toh, Kawamura, Shirouzu, Yamana, Kuwano, and Hideaki Tsuda. "Antineoplaston induces G1 arrest by PKCα and MAPK pathway in SKBR-3 breast cancer cells." Oncology Reports Oncology Reports 14 no. 2 (2005): 489-494.