Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells

Maksym Skrypnyk; Tetiana Yatsenko; Oleksandra Riabets; Yousef Salama; Margarita Skikevych; Taro Osada; Morikuni Tobita; Satoshi Takahashi; Koichi Hattori; Beate Heissig

doi:10.1016/j.heliyon.2024.e31777

Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells

Heliyon. 2024 May 29;10(11):e31777. doi: 10.1016/j.heliyon.2024.e31777. eCollection 2024 Jun 15.

Authors

Affiliations

¹ Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
² An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine.
³ Department of Surgical Dentistry and Maxillofacial Surgery with Plastic and Reconstructive Surgery of Head and Neck, Poltava State Medical University, 23 Shevchenko Street. Poltava, Ukraine.
⁴ Department of Gastroenterology Juntendo University Urayasu Hospital, Japan.
⁵ Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, Japan.
⁶ Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
⁷ Center for Genome and Regenerative Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.

Abstract

Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rβ, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis in vitro. N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with cyclin D downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and FasL in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.

Keywords: Adenocarcinoma; Apoptosis; Cytokine; Fas; Head and neck cancers; Interleukin-10; Interleukin-10 receptor; NF-kB; Reactive oxygen species; Salivary gland cancer; Salivary gland neoplasms; Tumor necrosis factor.