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Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells

Cancer is a multifactorial disease and hence can be effectively overcome by a multi-constituently therapeutic strategy. Medicinal plant extracts represent a perfect example of such stratagem. However, minimal studies have been done till date that portray the effect of extraction techniques on the ph...

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Autores principales: Sengupta, Pracheta, Raman, Sukanya, Chowdhury, Rajdeep, Lohitesh, K., Saini, Heena, Mukherjee, Sudeshna, Paul, Atish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732233/
https://www.ncbi.nlm.nih.gov/pubmed/29312880
http://dx.doi.org/10.3389/fonc.2017.00296
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author Sengupta, Pracheta
Raman, Sukanya
Chowdhury, Rajdeep
Lohitesh, K.
Saini, Heena
Mukherjee, Sudeshna
Paul, Atish
author_facet Sengupta, Pracheta
Raman, Sukanya
Chowdhury, Rajdeep
Lohitesh, K.
Saini, Heena
Mukherjee, Sudeshna
Paul, Atish
author_sort Sengupta, Pracheta
collection PubMed
description Cancer is a multifactorial disease and hence can be effectively overcome by a multi-constituently therapeutic strategy. Medicinal plant extracts represent a perfect example of such stratagem. However, minimal studies have been done till date that portray the effect of extraction techniques on the phyto-constituent profile of plant extracts and its impact on anticancer activity. In the present study, we have evaluated the anticancer potential of methanolic extracts of Berberis aristata root and Azadirachta indica seeds prepared by various extraction techniques in human osteosarcoma (HOS) cells. Soxhlation extract of B. aristata (BAM-SX) and sonication extract of A. indica (AIM-SO) were most effective in inducing apoptosis in parental drug sensitive, as well as resistant cell type developed by repeated drug exposure. Generation of reactive oxygen species and cell cycle arrest preceded caspase-mediated apoptosis in HOS cells. Interestingly, inhibition of autophagy enhanced cell death suggesting the cytoprotective role of autophagy. Combination studies of different methanolic extracts of BAM and AIM were performed, among which, the combination of BAM-SO and AIM-SO (BAAISO) was found to show synergism (IC(50) 10.27 µg/ml) followed by combination of BAM-MC and AIM-MC (BAAIMC) with respect to other combinations in the ratio of 1:1. BAAISO also showed synergism when it was added to cisplatin-resistant HOS cells (HCR). Chromatographic profiling of BAM-SX and AIM-SO by high performance thin layer chromatography resulted in identification of berberine (R(f) 0.55), palmitine (R(f) 0.50) in BAM-SX and azadirachtin A (R(f) 0.36), azadirachtin B (R(f) 0.56), nimbin (R(f) 0.80), and nimbolide (R(f) 0.43) in AIM-SO. The cytotoxic sensitivity obtained can be attributed to the above compounds. Our results highlight the importance of extraction technique and subsequent mechanism of action of multi-constituential B. aristata and A. indica against both sensitive and drug refractory HOS cells.
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spelling pubmed-57322332018-01-08 Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells Sengupta, Pracheta Raman, Sukanya Chowdhury, Rajdeep Lohitesh, K. Saini, Heena Mukherjee, Sudeshna Paul, Atish Front Oncol Oncology Cancer is a multifactorial disease and hence can be effectively overcome by a multi-constituently therapeutic strategy. Medicinal plant extracts represent a perfect example of such stratagem. However, minimal studies have been done till date that portray the effect of extraction techniques on the phyto-constituent profile of plant extracts and its impact on anticancer activity. In the present study, we have evaluated the anticancer potential of methanolic extracts of Berberis aristata root and Azadirachta indica seeds prepared by various extraction techniques in human osteosarcoma (HOS) cells. Soxhlation extract of B. aristata (BAM-SX) and sonication extract of A. indica (AIM-SO) were most effective in inducing apoptosis in parental drug sensitive, as well as resistant cell type developed by repeated drug exposure. Generation of reactive oxygen species and cell cycle arrest preceded caspase-mediated apoptosis in HOS cells. Interestingly, inhibition of autophagy enhanced cell death suggesting the cytoprotective role of autophagy. Combination studies of different methanolic extracts of BAM and AIM were performed, among which, the combination of BAM-SO and AIM-SO (BAAISO) was found to show synergism (IC(50) 10.27 µg/ml) followed by combination of BAM-MC and AIM-MC (BAAIMC) with respect to other combinations in the ratio of 1:1. BAAISO also showed synergism when it was added to cisplatin-resistant HOS cells (HCR). Chromatographic profiling of BAM-SX and AIM-SO by high performance thin layer chromatography resulted in identification of berberine (R(f) 0.55), palmitine (R(f) 0.50) in BAM-SX and azadirachtin A (R(f) 0.36), azadirachtin B (R(f) 0.56), nimbin (R(f) 0.80), and nimbolide (R(f) 0.43) in AIM-SO. The cytotoxic sensitivity obtained can be attributed to the above compounds. Our results highlight the importance of extraction technique and subsequent mechanism of action of multi-constituential B. aristata and A. indica against both sensitive and drug refractory HOS cells. Frontiers Media S.A. 2017-12-11 /pmc/articles/PMC5732233/ /pubmed/29312880 http://dx.doi.org/10.3389/fonc.2017.00296 Text en Copyright © 2017 Sengupta, Raman, Chowdhury, Lohitesh, Saini, Mukherjee and Paul. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sengupta, Pracheta
Raman, Sukanya
Chowdhury, Rajdeep
Lohitesh, K.
Saini, Heena
Mukherjee, Sudeshna
Paul, Atish
Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title_full Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title_fullStr Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title_full_unstemmed Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title_short Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
title_sort evaluation of apoptosis and autophagy inducing potential of berberis aristata, azadirachta indica, and their synergistic combinations in parental and resistant human osteosarcoma cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732233/
https://www.ncbi.nlm.nih.gov/pubmed/29312880
http://dx.doi.org/10.3389/fonc.2017.00296
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