Kaempferia parviflora Extract Inhibits STAT3 Activation and Interleukin-6 Production in HeLa Cervical Cancer Cells
by
Benjamart Suradej 1,2, Siriwoot Sookkhee 3, Jukreera Panyakaew 4, Pitchaya Mungkornasawakul 4,5, Nitwara Wikan 6, Duncan R. Smith 6
, Saranyapin Potikanond 1,7 and 
Wutigri Nimlamool 1,7,*
, Saranyapin Potikanond 1,7 and
Wutigri Nimlamool 1,7,*
1
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2
Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
3
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
4
Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
5
Environmental Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
6
Institute of Molecular Biosciences, Mahidol University, Salaya, Nakorn Pathom 73170, Thailand
7
Research Center of Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4226; https://doi.org/10.3390/ijms20174226
Received: 31 July 2019 / Revised: 23 August 2019 / Accepted: 27 August 2019 / Published: 29 August 2019
(This article belongs to the Special Issue Perspectives on the Health Benefits of Flavonoids)
Kaempferia parviflora (KP) has been reported to have anti-cancer activities. We previously reported its effects against cervical cancer cells and continued to elucidate the effects of KP on inhibiting the production and secretion of interleukin (IL)-6, as well as its relevant signaling pathways involved in cervical tumorigenesis. We discovered that KP suppressed epidermal growth factor (EGF)-induced IL-6 secretion in HeLa cells, and it was associated with a reduced level of Glycoprotein 130 (GP130), phosphorylated signal transducers and activators of transcription 3 (STAT3), and Mcl-1. Our data clearly showed that KP has no effect on nuclear factor kappa B (NF-κB) localization status. However, we found that KP inhibited EGF-stimulated phosphorylation of tyrosine 1045 and tyrosine 1068 of EGF receptor (EGFR) without affecting its expression level. The inhibition of EGFR activation was verified by the observation that KP significantly suppressed a major downstream MAP kinase, ERK1/2. Consistently, KP reduced the expression of Ki-67 protein, which is a cellular marker for proliferation. Moreover, KP potently inhibited phosphorylation of STAT3, Akt, and the expression of Mcl-1 in response to exogenous IL-6 stimulation. These data suggest that KP suppresses EGF-induced production of IL-6 and inhibits its autocrine IL-6/STAT3 signaling critical for maintaining cancer cell progression. We believe that KP may be a potential alternative anti-cancer agent for suppressing cervical tumorigenesis.
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Keywords:
anti-cancer; cervical cancer; Kaempferia parviflora; interleukin 6; STAT3 activation; EGFR phosphorylation; NF-κB
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MDPI and ACS Style
Suradej, B.; Sookkhee, S.; Panyakaew, J.; Mungkornasawakul, P.; Wikan, N.; Smith, D.R.; Potikanond, S.; Nimlamool, W. Kaempferia parviflora Extract Inhibits STAT3 Activation and Interleukin-6 Production in HeLa Cervical Cancer Cells. Int. J. Mol. Sci. 2019, 20, 4226.
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