Antiproliferative and Apoptotic Activities of Triterpenoid Saponins
                    from the Roots of Platycodon grandiflorum and Their Structure-Activity
                    Relationships

Jaemoo Chun; In Jin Ha; Yeong Shik Kim

doi:10.1055/s-0032-1328401

Planta Medica, Table of Contents

Planta Med 2013; 79(08): 639-645
DOI: 10.1055/s-0032-1328401

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Antiproliferative and Apoptotic Activities of Triterpenoid Saponins from the Roots of Platycodon grandiflorum and Their Structure-Activity Relationships

Jaemoo Chun

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea

,

In Jin Ha

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea

,

Yeong Shik Kim

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea

› Author Affiliations

Abstract

The present study was undertaken to investigate the antiproliferative and apoptotic activities of Platycodon saponins, including platycodin D, 2′′-O-acetylplatycodin D, 3′′-O-acetylplatycodin D, polygalacin D, 2′′-O-acetylpolygalacin D, and 3′′-O-acetylpolygalacin D, isolated from Platycodon grandiflorum, and prosapogenins which lack the C-3 or C-28 sugar residues, obtained from hydrolysis of platycodin D. We also clarified the structure-activity relationships of these molecules to define structural features that are crucial for the biological activity of Platycodon saponins and prosapogenins. The results showed that all Platycodon saponins had antiproliferative effects on the seven types of cancer cell lines tested. In particular, O-acetylation at the C-2 or C-3 position of rhamnose and dehydroxylation at C-24 increase the compoundʼs cytotoxicity, while the loss of sugar residues linked to C-3 or C-28 dramatically reduced cytotoxicity. This cytotoxicity was associated with apoptosis, which was indicated by DNA fragmentation, phosphatidylserine externalization, and the activation of caspases in AGS cells. Furthermore, Platycodon saponins suppressed the phosphorylation of Akt, which resulted in the inhibition of mTOR and NF-κB signaling following the inhibition of their downstream proteins. In conclusion, six Platycodon saponins have antiproliferative activity, and the presence of sugar residues, an O-acetyl group on the rhamnose, and a methyl group at C-4 contributes to their cytotoxicity and apoptotic activity. These findings may be useful in evaluating the structure-activity relationships of Platycodon saponins and modifying them as a potent apoptosis-inducing agent.

Key words

Platycodon grandiflorum - Campanulaceae - triterpenoid saponins - apoptosis - structure-activity relationships

Full Text

References

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