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Journal of Integrative Medicine ›› 2020, Vol. 18 ›› Issue (4): 326-333.doi: 10.1016/j.joim.2020.04.002

• Original Experimental Research • Previous Articles     Next Articles

In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma

Porwornwisit Tritripmongkola, Tullayakorn Plengsuriyakarna,b, Mayuri Tarasuka,b, Kesara Na-Bangchanga,b,c   

  1. a. Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand
    b. Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand
    c. Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Pathum Thani 12120, Thailand
  • Received:2019-11-08 Accepted:2019-08-05 Online:2020-07-10 Published:2020-04-22
  • Supported by:
    This study is funded by Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma of Thammasat University, and Thammasat University Research fund under the TU Research Scholar (Contract No.03/2561).

Objective
To evaluate the cytotoxic, apoptotic, mutagenic and immunomodulatory activities of Kaempferia galanga Linn. (KG) extract and ethyl-p-methoxycinnamate (EPMC) in vitro.

Methods
The present study investigated the cytotoxic [using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide test], apoptotic (using a mitochondrial membrane potential assay), mutagenic (using a micronucleus test) and immunomodulatory (using flow cytometry) activities of the ethanolic extract of KG and its bioactive component, EPMC, against two cholangiocarcinoma (CCA) cell lines, CL-6 and HuCCT1, and one normal human cell line, OUMS-36T-1F.

Results
Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells. The cytotoxic activity was supported by their concentration-dependent induction of apoptosis. CL-6 was most sensitive (3–4 fold) and selective to 5-fluorouracil (5-FU), compared with KG extract and EPMC [median half inhibiting concentration (IC50) and selectivity index (SI) were 23.01 μg/mL and 17.32; 78.41 μg/mL and 4.44; 100.76 μg/mL and 2.20, respectively for 5-FU vs. KG extract vs. EPMC]. HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract [median IC50 and SI were 66.03 μg/mL and 6.04; 60.90 μg/mL and 3.65; 156.60 μg/mL and 2.23, respectively for 5-FU vs. EPMC vs. KG extract]. EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells (IC50 = 92.20 μg/mL). KG extract and EPMC exhibited concentration-dependent mutagenic activity, as well as inhibition of tumor necrosis factor-α and interleukin-6.

Conclusion
Considering cytotoxic, apoptotic, immunomodulatory and mutagenic activities, further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.

Key words: Kaempferia galanga Linn, Cytotoxicity, Cholangiocarcinoma, Mutagenicity, Apoptosis, Immunomodulatory activity

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