PMID- 32418766 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20210917 IS - 2095-4964 (Print) VI - 18 IP - 4 DP - 2020 Jul TI - In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. PG - 326-333 LID - S2095-4964(20)30038-8 [pii] LID - 10.1016/j.joim.2020.04.002 [doi] AB - 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 (IC(50)) and selectivity index (SI) were 23.01 mug/mL and 17.32; 78.41 mug/mL and 4.44; 100.76 mug/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 IC(50) and SI were 66.03 mug/mL and 6.04; 60.90 mug/mL and 3.65; 156.60 mug/mL and 2.23, respectively for 5-FU vs. EPMC vs. KG extract]. EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells (IC(50) = 92.20 mug/mL). KG extract and EPMC exhibited concentration-dependent mutagenic activity, as well as inhibition of tumor necrosis factor-alpha 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. CI - Copyright (c) 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved. FAU - Tritripmongkol, Porwornwisit AU - Tritripmongkol P AD - Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Plengsuriyakarn, Tullayakorn AU - Plengsuriyakarn T AD - Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Tarasuk, Mayuri AU - Tarasuk M AD - Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Na-Bangchang, Kesara AU - Na-Bangchang K AD - Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Pathum Thani 12120, Thailand. Electronic address: Kesaratmu@yahoo.com. LA - eng PT - Journal Article DEP - 20200422 PL - Netherlands TA - J Integr Med JT - Journal of integrative medicine JID - 101603118 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Plant Extracts) SB - IM MH - Antineoplastic Agents, Phytogenic/*pharmacology MH - *Bile Duct Neoplasms/drug therapy/pathology MH - Cell Line, Tumor/drug effects MH - *Cholangiocarcinoma/drug therapy/pathology MH - Humans MH - Plant Extracts/*pharmacology MH - *Zingiberaceae/chemistry OTO - NOTNLM OT - Apoptosis OT - Cholangiocarcinoma OT - Cytotoxicity OT - Immunomodulatory activity OT - Kaempferia galanga Linn. OT - Mutagenicity EDAT- 2020/05/19 06:00 MHDA- 2021/09/18 06:00 CRDT- 2020/05/19 06:00 PHST- 2019/08/05 00:00 [received] PHST- 2019/12/08 00:00 [accepted] PHST- 2020/05/19 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2020/05/19 06:00 [entrez] AID - S2095-4964(20)30038-8 [pii] AID - 10.1016/j.joim.2020.04.002 [doi] PST - ppublish SO - J Integr Med. 2020 Jul;18(4):326-333. doi: 10.1016/j.joim.2020.04.002. Epub 2020 Apr 22.