Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN
Objective: To investigate the anticancer potential of a novel synthetic derivative of a naturally occurring diterpenoid against glioblastoma. Method: The in vitro study was conducted at the Ojha Campus of Dow University of Health Sciences, Karachi, from February to December 2021, and comprised U87...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Pakistan Medical Association
2024-02-01
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| Series: | Journal of the Pakistan Medical Association |
| Online Access: | http://ojs.jpma.org.pk/index.php/public_html/article/view/1163 |
| _version_ | 1797219497694724096 |
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| author | Shafea Saad Farina Hanif Shabana Usman Simjee Shaheen Faizi Lubna Khan Ambreen Ashfaque |
| author_facet | Shafea Saad Farina Hanif Shabana Usman Simjee Shaheen Faizi Lubna Khan Ambreen Ashfaque |
| author_sort | Shafea Saad |
| collection | DOAJ |
| description |
Objective: To investigate the anticancer potential of a novel synthetic derivative of a naturally occurring
diterpenoid against glioblastoma.
Method: The in vitro study was conducted at the Ojha Campus of Dow University of Health Sciences, Karachi, from
February to December 2021, and comprised U87 cells. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay was used to determine the growth inhibitory effect of 16(R and S) – phenylamino-cleroda3, 13(14) Zdiene-
15, 16 olide and standard drug temozolomide against glioblastoma cells, and half-maximal inhibitory
concentration was calculated. Microscopy and immunocytochemistry were used to investigate apoptotic
morphology and active caspase-3 and B-cell lymphoma 2 (Bcl-2) expression. Quantitative real time polymerase
chain reaction was used to investigate the expression of proliferation markers. Data was analysed using SPSS 21.
Results: Both the synthetic derivative and the standard drug significantly inhibited growth of U87 cells (p<0.001)
with half-maximal inhibitory concentration of 19uM and 185uM, respectively. Apoptotic morphology and
upregulation of active caspase-3 protein expression was observed in cells treated with half-maximal inhibitory
concentration doses of both the synthetic derivative (p<0.05) and the standard drug (p<0.001), and Bcl-2 was downregulated
in both the synthetic derivative (p<0.01) and the standard drug (p=0.05). However, no significant
difference was observed in the expression of proliferation markers (p>0.05).
Conclusion: The synthetic diterpene derivative PGEA-AN showed growth inhibitory actiity against glioblastoma.
Key Words: Temozolomide, Caspase, Glioblastoma, Diterpenes.
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| first_indexed | 2024-04-24T12:34:35Z |
| format | Article |
| id | doaj.art-f6ca8ef75c7f4023a75457bb3ca18837 |
| institution | Directory Open Access Journal |
| issn | 0030-9982 |
| language | English |
| last_indexed | 2024-04-24T12:34:35Z |
| publishDate | 2024-02-01 |
| publisher | Pakistan Medical Association |
| record_format | Article |
| series | Journal of the Pakistan Medical Association |
| spelling | doaj.art-f6ca8ef75c7f4023a75457bb3ca188372024-04-07T16:28:14ZengPakistan Medical AssociationJournal of the Pakistan Medical Association0030-99822024-02-01742Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-ANShafea Saad0Farina Hanif1Shabana Usman Simjee2Shaheen Faizi3Lubna Khan4Ambreen Ashfaque5Department of Physiology, Dow International Medical College, Dow University of Health SciencesDepartment of Biochemistry, Dow International Medical College, Dow University of Health Sciences,H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi,H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, PakistanDepartment of Biotechnology, University of Karachi, Karachi, PakistanDepartment of Physiology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan Objective: To investigate the anticancer potential of a novel synthetic derivative of a naturally occurring diterpenoid against glioblastoma. Method: The in vitro study was conducted at the Ojha Campus of Dow University of Health Sciences, Karachi, from February to December 2021, and comprised U87 cells. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the growth inhibitory effect of 16(R and S) – phenylamino-cleroda3, 13(14) Zdiene- 15, 16 olide and standard drug temozolomide against glioblastoma cells, and half-maximal inhibitory concentration was calculated. Microscopy and immunocytochemistry were used to investigate apoptotic morphology and active caspase-3 and B-cell lymphoma 2 (Bcl-2) expression. Quantitative real time polymerase chain reaction was used to investigate the expression of proliferation markers. Data was analysed using SPSS 21. Results: Both the synthetic derivative and the standard drug significantly inhibited growth of U87 cells (p<0.001) with half-maximal inhibitory concentration of 19uM and 185uM, respectively. Apoptotic morphology and upregulation of active caspase-3 protein expression was observed in cells treated with half-maximal inhibitory concentration doses of both the synthetic derivative (p<0.05) and the standard drug (p<0.001), and Bcl-2 was downregulated in both the synthetic derivative (p<0.01) and the standard drug (p=0.05). However, no significant difference was observed in the expression of proliferation markers (p>0.05). Conclusion: The synthetic diterpene derivative PGEA-AN showed growth inhibitory actiity against glioblastoma. Key Words: Temozolomide, Caspase, Glioblastoma, Diterpenes. http://ojs.jpma.org.pk/index.php/public_html/article/view/1163 |
| spellingShingle | Shafea Saad Farina Hanif Shabana Usman Simjee Shaheen Faizi Lubna Khan Ambreen Ashfaque Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN Journal of the Pakistan Medical Association |
| title | Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN |
| title_full | Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN |
| title_fullStr | Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN |
| title_full_unstemmed | Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN |
| title_short | Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN |
| title_sort | modulation of apoptotic and akt pi3k mtor pathways to target glioblastoma cells using synthetic compound pgea an |
| url | http://ojs.jpma.org.pk/index.php/public_html/article/view/1163 |
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