Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells

Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of...

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Main Authors: Saranyapin Potikanond, Siriwoot Sookkhee, Mingkwan Na Takuathung, Pitchaya Mungkornasawakul, Nitwara Wikan, Duncan R. Smith, Wutigri Nimlamool
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2017.00630/full
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author Saranyapin Potikanond
Siriwoot Sookkhee
Mingkwan Na Takuathung
Pitchaya Mungkornasawakul
Pitchaya Mungkornasawakul
Nitwara Wikan
Duncan R. Smith
Wutigri Nimlamool
author_facet Saranyapin Potikanond
Siriwoot Sookkhee
Mingkwan Na Takuathung
Pitchaya Mungkornasawakul
Pitchaya Mungkornasawakul
Nitwara Wikan
Duncan R. Smith
Wutigri Nimlamool
author_sort Saranyapin Potikanond
collection DOAJ
description Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow tumor progression and metastasis in patients with cervical cancer. Taken together, the present report provides accumulated evidence revealing the potent anti-cancer activities of Kaempferia parviflora against cervical cancer HeLa cells, and suggests its potential use as an alternative way for cervical cancer prevention and therapy.
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spelling doaj.art-675cace19a7346f6ba6868bda04f93f12022-12-21T22:27:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-09-01810.3389/fphar.2017.00630296967Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer CellsSaranyapin Potikanond0Siriwoot Sookkhee1Mingkwan Na Takuathung2Pitchaya Mungkornasawakul3Pitchaya Mungkornasawakul4Nitwara Wikan5Duncan R. Smith6Wutigri Nimlamool7Department of Pharmacology, Faculty of Medicine, Chiang Mai UniversityChiang Mai, ThailandDepartment of Microbiology, Faculty of Medicine, Chiang Mai UniversityChiang Mai, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai UniversityChiang Mai, ThailandDepartment of Chemistry, Faculty of Science, Chiang Mai UniversityChiang Mai, ThailandEnvironmental Science Program, Faculty of Science, Chiang Mai UniversityChiang Mai, ThailandInstitute of Molecular Biosciences, Mahidol UniversityNakorn Pathom, ThailandInstitute of Molecular Biosciences, Mahidol UniversityNakorn Pathom, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai UniversityChiang Mai, ThailandKaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow tumor progression and metastasis in patients with cervical cancer. Taken together, the present report provides accumulated evidence revealing the potent anti-cancer activities of Kaempferia parviflora against cervical cancer HeLa cells, and suggests its potential use as an alternative way for cervical cancer prevention and therapy.http://journal.frontiersin.org/article/10.3389/fphar.2017.00630/fullanti-cancerapoptosiscervical cancerinvasionKaempferia parvifloraMAPK pathway
spellingShingle Saranyapin Potikanond
Siriwoot Sookkhee
Mingkwan Na Takuathung
Pitchaya Mungkornasawakul
Pitchaya Mungkornasawakul
Nitwara Wikan
Duncan R. Smith
Wutigri Nimlamool
Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
Frontiers in Pharmacology
anti-cancer
apoptosis
cervical cancer
invasion
Kaempferia parviflora
MAPK pathway
title Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
title_full Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
title_fullStr Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
title_full_unstemmed Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
title_short Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells
title_sort kaempferia parviflora extract exhibits anti cancer activity against hela cervical cancer cells
topic anti-cancer
apoptosis
cervical cancer
invasion
Kaempferia parviflora
MAPK pathway
url http://journal.frontiersin.org/article/10.3389/fphar.2017.00630/full
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