Open Access

RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells

  • Authors:
    • Yukiko Kariya
    • Takeo Tatsuta
    • Shigeki Sugawara
    • Yoshinobu Kariya
    • Kazuo Nitta
    • Masahiro Hosono
  • View Affiliations

  • Published online on: August 11, 2016     https://doi.org/10.3892/ijo.2016.3656
  • Pages: 1334-1342
  • Copyright: © Kariya et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sialic acid-binding lectin obtained from bullfrog eggs (SBL) induces cell death in cancer cells but not in normal cells. This antitumor effect is mediated through its ribonuclease (RNase) activity. However, the underlying molecular mechanisms remain unclear. We found that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated when SBL induced cell death in three human breast cancer cell lines: SK-BR-3, MCF-7, and MDA‑MB231. The suppression of p38 MAPK phosphorylation by a p38 MAPK inhibitor as well as short interference RNA knockdown of p38 MAPK expression significantly decreased cell death and increased the cell viability of SBL-treated MDA‑MB231 cells. H103A, an SBL mutant lacking in RNase activity, showed decreased SBL-induced cell death compared with native SBL. However, the loss of RNase activity of SBL had no effect on its internalization into cells. The H103A mutant also displayed decreased phosphorylation of p38 MAPK. Moreover, SBL promoted caspase‑3/7 activation followed by a cleavage of poly (ADP-ribose)-polymerase, whereas the SBL mutant, H103A, lost this ability. The SBL-induced caspase‑3/7 activation was suppressed by the p38 MAPK inhibitor, SB203580, as well as pan-caspase inhibitor, zVAD-fmk. In the presence of zVAD-fmk, the SBL-induced cell death was decreased. In addition, the cell viability of SBL-treated MDA‑MB231 cells recovered by zVAD-fmk treatment. Taken together, our results suggest that the RNase activity of SBL leads to breast cancer cell death through the activation of p38 MAPK followed by the activation of caspase‑3/7.
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October-2016
Volume 49 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kariya Y, Tatsuta T, Sugawara S, Kariya Y, Nitta K and Hosono M: RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells. Int J Oncol 49: 1334-1342, 2016.
APA
Kariya, Y., Tatsuta, T., Sugawara, S., Kariya, Y., Nitta, K., & Hosono, M. (2016). RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells. International Journal of Oncology, 49, 1334-1342. https://doi.org/10.3892/ijo.2016.3656
MLA
Kariya, Y., Tatsuta, T., Sugawara, S., Kariya, Y., Nitta, K., Hosono, M."RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells". International Journal of Oncology 49.4 (2016): 1334-1342.
Chicago
Kariya, Y., Tatsuta, T., Sugawara, S., Kariya, Y., Nitta, K., Hosono, M."RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells". International Journal of Oncology 49, no. 4 (2016): 1334-1342. https://doi.org/10.3892/ijo.2016.3656