5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3)

Yu-Chieh Su; Chih-Chun Wang; Jui-Hsi Weng; Shyh-An Yeh; Po-Jen Chen; Tzer-Zen Hwang; Huang-Chi Chen

doi:10.3389/fonc.2022.834941

5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3)

Front Oncol. 2022 Jul 22:12:834941. doi: 10.3389/fonc.2022.834941. eCollection 2022.

Authors

Yu-Chieh Su^{1

2}, Chih-Chun Wang^{1

3}, Jui-Hsi Weng⁴, Shyh-An Yeh^{5

6}, Po-Jen Chen⁷, Tzer-Zen Hwang^{1

3}, Huang-Chi Chen^{8

9}

Affiliations

¹ School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
² Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
³ Department of Otolaryngology, E-Da Hospital, Kaohsiung, Taiwan.
⁴ Yuh-Ing Junior College of Health Care and Management, Kaohsiung, Taiwan.
⁵ Department of Radiation Oncology, E-Da Hospital, Kaohsiung, Taiwan.
⁶ Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung City, Taiwan.
⁷ Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.
⁸ Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common cancer of the oral cavity. Cisplatin (CDDP) is the ideal chemo-radiotherapy used for several tumor types, but resistance to the drug has become a major obstacle in treating patients with HNSCC. 5-methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, reduces inflammation-mediated proliferation and metastasis. This study aimed to assess the anti-oral cancer activity of 5-MTP when used alone or in combination with CDDP. Results showed that CDDP dose dependently reduced the growth of SSC25 cells but not 5-MTP. The combination of CDDP and 5-MTP exerted additional inhibitory effect on the growth of SSC25 cells by attenuating the phosphorylation of STAT3. In the 4-nitroquinoline-1-oxide-induced oral cancer mouse model, 5-MTP sensitized the reduction effect of CDDP on tumorigenesis, which restricted the tongue tissue in hyperkeratotic lesion rather than squamous cell carcinoma. The combination of CDDP and 5-MTP may be a potent therapeutic strategy for HNSCC patients with radiotherapy.

Keywords: 4NQO; 5-methoxytryptophan; STAT3; cisplatin; head and neck squamous cell carcinoma.