Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells
Objective: Nature has provided us with many pharmaceutical resources so far. Breast cancer shows an increasing trend in the world for the last decade and becomes one of five leading causes of death. Among the plants, Melia azedarach L. has been used widely in traditional medicine for many ailments i...
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Asian Pacific Organization for Cancer Prevention
2021
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id-langga.1254602023-04-29T03:20:21Z https://repository.unair.ac.id/125460/ Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells Martha Ervina, - Hadi Poerwono, - Retno Widyowati, - Hideaki Otsuka, - Katsuyoshi Matsunami, - Sukardiman, - R Medicine RS Pharmacy and materia medica RS1-441 Pharmacy and materia medica RS200-201 Pharmaceutical dosage forms Objective: Nature has provided us with many pharmaceutical resources so far. Breast cancer shows an increasing trend in the world for the last decade and becomes one of five leading causes of death. Among the plants, Melia azedarach L. has been used widely in traditional medicine for many ailments including breast cancer. Following our previous findings that the ethyl acetate fraction was the most active cytotoxic fraction against T47D cells, we aimed to isolate the cytotoxic compounds and further elucidate their apoptotic mechanisms. Methods: The compounds were isolated through a series of chromatography with cytotoxicity evaluations. Identification of the isolated compounds was achieved by intensive spectroscopic analysis such as NMR, MS, and IR spectra. Cytotoxicity was evaluated by MTT method using doxorubicin as a reference compound. The expression of apoptosis-related factors was quantified by flow cytometry and immunocytochemistry. Results: Two isomers of pregnane steroids with molecular weight 330.2087 (C21H30O3) were isolated from the EtOAc extract. Spectroscopic analysis revealed the structures as 17-ethylene-3,4-dihydroxy-14-methyl-18-norandrostene-16-one (1) and 17-ethylene-3,4-dihydroxy-5-pregnene-16-one (2), respectively. These compounds showed moderate cytotoxicity (IC50 172.9 and 62.2 µg/mL, respectively) comparable to doxorubicin (IC50 3.08 µg/mL). The execution of apoptosis may be related to the increase of the ratio of BAX/bcl-2 of the cells. Conclusion: The EtOAc fraction of Melia azedarach L. leaves and the isolated 5-pregnene-16-one steroids are promising reagents for breast cancer treatment by introducing apoptosis to tumor cells. However, further researches are required to highlight its safety and usage in vivo. Asian Pacific Organization for Cancer Prevention 2021-06-01 Article PeerReviewed text en https://repository.unair.ac.id/125460/1/C-15_artikel.pdf text en https://repository.unair.ac.id/125460/2/Kualitas%20Karil%20C-15.pdf text en https://repository.unair.ac.id/125460/3/C-15_similarity.pdf Martha Ervina, - and Hadi Poerwono, - and Retno Widyowati, - and Hideaki Otsuka, - and Katsuyoshi Matsunami, - and Sukardiman, - (2021) Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells. Asian Pacific Journal of Cancer Prevention, 22 (6). pp. 1967-1973. ISSN 1513-7368 http://journal.waocp.org/article_89651.html https://doi.org/10.31557/APJCP.2021.22.6.1967 |
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R Medicine RS Pharmacy and materia medica RS1-441 Pharmacy and materia medica RS200-201 Pharmaceutical dosage forms Martha Ervina, - Hadi Poerwono, - Retno Widyowati, - Hideaki Otsuka, - Katsuyoshi Matsunami, - Sukardiman, - Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
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Objective: Nature has provided us with many pharmaceutical resources so far. Breast cancer shows an increasing trend in the world for the last decade and becomes one of five leading causes of death. Among the plants, Melia azedarach L. has been used widely in traditional medicine for many ailments including breast cancer. Following our previous findings that the ethyl acetate fraction was the most active cytotoxic fraction against T47D cells, we aimed to isolate the cytotoxic compounds and further elucidate their apoptotic mechanisms. Methods: The compounds were isolated through a series of chromatography with cytotoxicity evaluations. Identification of the isolated compounds was achieved by intensive spectroscopic analysis such as NMR, MS, and IR spectra. Cytotoxicity was evaluated by MTT method using doxorubicin as a reference compound. The expression of apoptosis-related factors was quantified by flow cytometry and immunocytochemistry. Results: Two isomers of pregnane steroids with molecular weight 330.2087 (C21H30O3) were isolated from the EtOAc extract. Spectroscopic analysis revealed the structures as 17-ethylene-3,4-dihydroxy-14-methyl-18-norandrostene-16-one (1) and 17-ethylene-3,4-dihydroxy-5-pregnene-16-one (2), respectively. These compounds showed moderate cytotoxicity (IC50 172.9 and 62.2 µg/mL, respectively) comparable to doxorubicin (IC50 3.08 µg/mL). The execution of apoptosis may be related to the increase of the ratio of BAX/bcl-2 of the cells. Conclusion: The EtOAc fraction of Melia azedarach L. leaves and the isolated 5-pregnene-16-one steroids are promising reagents for breast cancer treatment by introducing apoptosis to tumor cells. However, further researches are required to highlight its safety and usage in vivo. |
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Martha Ervina, - Hadi Poerwono, - Retno Widyowati, - Hideaki Otsuka, - Katsuyoshi Matsunami, - Sukardiman, - |
author_facet |
Martha Ervina, - Hadi Poerwono, - Retno Widyowati, - Hideaki Otsuka, - Katsuyoshi Matsunami, - Sukardiman, - |
author_sort |
Martha Ervina, - |
title |
Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
title_short |
Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
title_full |
Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
title_fullStr |
Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
title_full_unstemmed |
Pregnane Steroids from the Leaves of Melia azedarach and Apoptotic Activity against T47D Cells |
title_sort |
pregnane steroids from the leaves of melia azedarach and apoptotic activity against t47d cells |
publisher |
Asian Pacific Organization for Cancer Prevention |
publishDate |
2021 |
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https://repository.unair.ac.id/125460/1/C-15_artikel.pdf https://repository.unair.ac.id/125460/2/Kualitas%20Karil%20C-15.pdf https://repository.unair.ac.id/125460/3/C-15_similarity.pdf https://repository.unair.ac.id/125460/ http://journal.waocp.org/article_89651.html https://doi.org/10.31557/APJCP.2021.22.6.1967 |
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