Sodium Danshensu Inhibits Oral Cancer Cell Migration and Invasion by Modulating p38 Signaling Pathway

  • Front Endocrinol (Lausanne). 2020 Sep 30:11:568436. doi: 10.3389/fendo.2020.568436.
V Bharath Kumar  1 ,  Shu-Hui Lin  2  3 ,  B Mahalakshmi  4 ,  Yu-Sheng Lo  5 ,  Chia-Chieh Lin  5 ,  Yi-Ching Chuang  5 ,  Ming-Ju Hsieh  5  6  7  8 ,  Mu-Kuan Chen  9
Affiliations
  • 1. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
  • 2. Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.
  • 3. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
  • 4. Institute of Research and Development, Duy Tan University, Da Nang, Vietnam.
  • 5. Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
  • 6. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • 7. Department of Holistic Wellness, Mingdao University, Changhua, Taiwan.
  • 8. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
  • 9. Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan.
PMID: 33101201 DOI: 10.3389/fendo.2020.568436
Abstract

Background: Oral squamous cell carcinoma (OSCC) that comprises about 90% of all oral Cancer cases is associated with poor prognosis due to its highly metastatic nature. The majority of OSCC treatment options are related detrimental side-effects. Hypothesis/Purpose: The present study aimed at deciphering the effects of a bioactive phytochemical, sodium danshensu, on human oral Cancer cell metastasis. Methods and Results: The treatment of FaDu and Ca9-22 cells with different doses of sodium danshensu (25, 50, and 100 μM) caused a significant reduction in cellular motility, migration, and invasion, as compared to the untreated cells. This effect was associated with a reduced expression of MMP-2, vimentin and N-Cadherin, together with an enhanced expression of E-cadherin and ZO-1. Further investigation on the molecular mechanism revealed that treatment with sodium danshensu caused significant reduction in p38 phosphorylation; however, phosphorylation of ERK1/2 significantly decreased only in FaDu cells, whereas p-JNK1/2 did not show any alteration. A combination of p38 and JNK1/2 inhibitors with sodium danshensu also reduced the migration in the FaDu and Ca9-22 cell lines. Conclusion: Collectively, the present study findings reveal that sodium danshensu execute anti-metastatic effect by suppressing p38 phosphorylation in human oral Cancer. The study identifies sodium danshensu as a potential natural Anticancer agent that can be used therapeutically to manage highly metastatic OSCC.

Keywords
P38 signaling pathway; invasion; migration; oral squamous cell carcinoma (OSCC); sodium danshensu (Pubchem CID: 23711819).
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