Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines

Tomoyuki Tano, Masato Okamoto, Shin Kan, Koh Ichi Nakashiro, Shigetaka Shimodaira, Naomi Yamashita, Yutaka Kawakami, Hiroyuki Hamakawa

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Toll-like receptor 4 (TLR4) plays a significant role in cancer therapy as receptors of bacteria-derived immunotherapeutic agents such as OK-432, a streptococcal immunotherapeutic agent. In addition, recent reports demonstrated that TLRs, including TLR4, are also expressed in cancer cells as well as in immunocompetent cells. It is a problem in cancer therapy that the immunoadjuvant may activate survival signals such as nuclear factor (NF)-κB or mitogen-activated protein kinases (MAPKs) in cancer cells via TLRs. In the current study, we investigated responsiveness of human head and neck cancer cell lines against TLR4 ligands, OK-PSA, an active component of OK-432, and a lipopolysaccharide (LPS). Stimulation with LPS or OK-PSA resulted in the activation of NF-κB in these cell lines expressing TLR4 and MD-2 that is a significant coreceptor for TLR4 signaling. Interestingly, OK-PSA induced cell-growth inhibition, while LPS enhanced the proliferation of the cancer cells. OK-PSA induced NF-κB activation more slowly than that induced by LPS. In addition, phosphorylation of p38 MAPK by OK-PSA was only slight compared with that by LPS. OK-PSA also induced apoptosis of the cancer cells mediated by the activation of caspase 1, 3 and 8 in a p53-independent manner. These findings strongly suggest that active components of OK-432 may elicit anti-cancer effects via enhancing host immunity as well as via directly inducing the growth inhibition and apoptosis of head and neck cancer cells through TLR4 signal.

Original languageEnglish
Pages (from-to)678-685
Number of pages8
JournalOral Oncology
Volume48
Issue number8
DOIs
Publication statusPublished - 2012 Aug 1
Externally publishedYes

Keywords

  • Apoptosis
  • Head and neck cancer cells
  • OK-432
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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