Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach

<i>Background and Objectives:</i> Natural products have proven to be a valuable source for the discovery of new candidate drugs for cancer treatment. This study aims to investigate the potential therapeutic effects of “Kerra™”, a natural extract derived from a mixture of nine medicinal p...

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Main Authors: Jeeraprapa Siriwaseree, Yodying Yingchutrakul, Pawitrabhorn Samutrtai, Chanat Aonbangkhen, Pussadee Srathong, Sucheewin Krobthong, Kiattawee Choowongkomon
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1648-9144/59/8/1376
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author Jeeraprapa Siriwaseree
Yodying Yingchutrakul
Pawitrabhorn Samutrtai
Chanat Aonbangkhen
Pussadee Srathong
Sucheewin Krobthong
Kiattawee Choowongkomon
author_facet Jeeraprapa Siriwaseree
Yodying Yingchutrakul
Pawitrabhorn Samutrtai
Chanat Aonbangkhen
Pussadee Srathong
Sucheewin Krobthong
Kiattawee Choowongkomon
author_sort Jeeraprapa Siriwaseree
collection DOAJ
description <i>Background and Objectives:</i> Natural products have proven to be a valuable source for the discovery of new candidate drugs for cancer treatment. This study aims to investigate the potential therapeutic effects of “Kerra™”, a natural extract derived from a mixture of nine medicinal plants mentioned in the ancient Thai scripture named the <i>Takxila Scripture</i>, on HCT116 cells. <i>Materials and Methods:</i> In this study, the effect of the Kerra™ extract on cancer cells was assessed through cell viability assays. Apoptotic activity was evaluated by examining the apoptosis characteristic features. A proteomics analysis was conducted to identify proteins and pathways associated with the extract’s mechanism of action. The expression levels of apoptotic protein markers were measured to validate the extract’s efficacy. <i>Results:</i> The Kerra™ extract demonstrated a dose-dependent inhibitory effect on the cells, with higher concentrations leading to decreased cell viability. Treatment with the extract for 72 h induced characteristic features of early and late apoptosis, as well as cell death. An LC-MS/MS analysis identified a total of 3406 proteins. The pathway analysis revealed that the Kerra™ extract stimulated apoptosis and cell death in colorectal cancer cell lines and suppressed cell proliferation in adenocarcinoma cell lines through the EIF2 signaling pathway. Upstream regulatory proteins, including cyclin-dependent kinase inhibitor 1A (CDKN1A) and MYC proto-oncogene, bHLH transcription factor (MYC), were identified. The expressions of caspase-8 and caspase-9 were significantly elevated by the Kerra™ extract compared to the chemotherapy drug Doxorubicin (Dox). <i>Conclusions:</i> These findings provide strong evidence for the ability of the Kerra™ extract to induce apoptosis in HCT116 colon cancer cells. The extract’s efficacy was demonstrated by its dose-dependent inhibitory effect, induction of apoptotic activity, and modulation of key proteins involved in cell death and proliferation pathways. This study highlights the potential of Kerra™ as a promising therapeutic agent in cancer treatment.
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spelling doaj.art-7874fa1a252e40eeacb4bc54d0a120e02023-11-19T02:05:15ZengMDPI AGMedicina1010-660X1648-91442023-07-01598137610.3390/medicina59081376Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics ApproachJeeraprapa Siriwaseree0Yodying Yingchutrakul1Pawitrabhorn Samutrtai2Chanat Aonbangkhen3Pussadee Srathong4Sucheewin Krobthong5Kiattawee Choowongkomon6Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, ThailandNational Center for Genetic Engineering and Biotechnology, NSTDA, Pathum Thani 12120, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Excellence in Natural Products Chemistry (CENP), Department of Chemistry Faculty of Science, Chulalongkorn University, Bangkok 10330, ThailandFaculty of Nursing, Praboromarajchanok Institute, Nonthaburi 11000, ThailandCenter of Excellence in Natural Products Chemistry (CENP), Department of Chemistry Faculty of Science, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand<i>Background and Objectives:</i> Natural products have proven to be a valuable source for the discovery of new candidate drugs for cancer treatment. This study aims to investigate the potential therapeutic effects of “Kerra™”, a natural extract derived from a mixture of nine medicinal plants mentioned in the ancient Thai scripture named the <i>Takxila Scripture</i>, on HCT116 cells. <i>Materials and Methods:</i> In this study, the effect of the Kerra™ extract on cancer cells was assessed through cell viability assays. Apoptotic activity was evaluated by examining the apoptosis characteristic features. A proteomics analysis was conducted to identify proteins and pathways associated with the extract’s mechanism of action. The expression levels of apoptotic protein markers were measured to validate the extract’s efficacy. <i>Results:</i> The Kerra™ extract demonstrated a dose-dependent inhibitory effect on the cells, with higher concentrations leading to decreased cell viability. Treatment with the extract for 72 h induced characteristic features of early and late apoptosis, as well as cell death. An LC-MS/MS analysis identified a total of 3406 proteins. The pathway analysis revealed that the Kerra™ extract stimulated apoptosis and cell death in colorectal cancer cell lines and suppressed cell proliferation in adenocarcinoma cell lines through the EIF2 signaling pathway. Upstream regulatory proteins, including cyclin-dependent kinase inhibitor 1A (CDKN1A) and MYC proto-oncogene, bHLH transcription factor (MYC), were identified. The expressions of caspase-8 and caspase-9 were significantly elevated by the Kerra™ extract compared to the chemotherapy drug Doxorubicin (Dox). <i>Conclusions:</i> These findings provide strong evidence for the ability of the Kerra™ extract to induce apoptosis in HCT116 colon cancer cells. The extract’s efficacy was demonstrated by its dose-dependent inhibitory effect, induction of apoptotic activity, and modulation of key proteins involved in cell death and proliferation pathways. This study highlights the potential of Kerra™ as a promising therapeutic agent in cancer treatment.https://www.mdpi.com/1648-9144/59/8/1376traditional herbsLC-MS/MScolorectal cancercaspase-8caspase-9CDKN1A
spellingShingle Jeeraprapa Siriwaseree
Yodying Yingchutrakul
Pawitrabhorn Samutrtai
Chanat Aonbangkhen
Pussadee Srathong
Sucheewin Krobthong
Kiattawee Choowongkomon
Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
Medicina
traditional herbs
LC-MS/MS
colorectal cancer
caspase-8
caspase-9
CDKN1A
title Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
title_full Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
title_fullStr Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
title_full_unstemmed Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
title_short Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach
title_sort exploring the apoptotic induced biochemical mechanism of traditional thai herb kerra™ extract in hct116 cells using a label free proteomics approach
topic traditional herbs
LC-MS/MS
colorectal cancer
caspase-8
caspase-9
CDKN1A
url https://www.mdpi.com/1648-9144/59/8/1376
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