| In vitro: |
| Int J Oncol. 2014 Aug;45(2):757-63. | | The anticancer effect and mechanism of α-hederin on breast cancer cells.[Pubmed: 24842044] | Natural plant products occupy a very important position in the area of cancer chemotherapy. Many triterpenoid saponins have been proved as potential agents for chemoprevention and therapy of breast cancer.
alpha-Hederin, a monodesmosidic triterpenoid saponin distributed in Hedera or Nigella species, displays many biological activities. It is increasingly investigated for its promising anticancer potential since it has been shown to have cytotoxicity against several types of cancer cells. However, studies of alpha-Hederin on breast cancer are limited, most of which focus on biological activity, while the mechanisms have not been widely reported yet. Previously, we purified and identified alpha-Hederin from Clematis ganpiniana, a herb used in traditional Chinese medicine with antitumor action.
CONCLUSIONS:
In the present study, alpha-Hederin showed strong inhibitory activity on the growth of breast cancer cells and induced apoptosis in these cells. alpha-Hederin induced depolarization of mitochondrial membrane potential which released Apaf-1 and cytochrome c from the intermembrane space into the cytosol, where they promoted caspase-3 and caspase-9 activation.
CONCLUSIONS:
This is the first report on the growth inhibition and pro-apoptotic effects of alpha-Hederin on breast cancer cells and the relative apoptosis pathways. It implied that triterpenoid saponin alpha-Hederin could be a promising candidate for chemotherapy of breast cancer. | | Phytochemistry. 2014 May;101:116-20. | | The haploinsufficiency profile of α-hederin suggests a caspofungin-like antifungal mode of action.[Pubmed: 24569176 ] | The leaves of common ivy (Hedera helix) contain the cytotoxic saponin alpha-Hederin, which is inhibitory to Candida albicans at low concentrations.
METHODS AND RESULTS:
To investigate the mode of action of alpha-Hederin, a haploinsufficiency screen was carried out using a library of 1152 Saccharomyces cerevisiae deletion strains. An ethanol ivy extract containing alpha-Hederin was used in the initial screen to reduce the amount of compound required. Strains exhibiting disproportionately low growth were then examined in more detail by comparing growth curves in the presence and absence of alpha-Hederin. This approach identified three hypersensitive strains carrying gene deletions for components of the transcription related proteins SWI/SNF, RNA polymerase II and the RSC complex. Saponin cytotoxicity is often attributed to membrane damage, however alpha-Hederin did not induce hypersensitivity with an aminophospholipid translocase deletion strain that is frequently hypersensitive to membrane damaging agents.
CONCLUSIONS:
The haploinsufficiency profile of alpha-Hederin is most similar to that reported for drugs such as caspofungin that inhibit synthesis of the fungal cell wall. | | Planta Med. 2004 Jun;70(6):561-3. | | Antioxidant activity of saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F.[Pubmed: 15241892] | The antioxidant activities of alpha-hederin and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F from Hedera colchica were investigated, in this study.
METHODS AND RESULTS:
The antioxidant properties of the saponins were evaluated using different antioxidant tests: 1,1-di-phenyl-2-picryl-hydrazyl (DPPH.) free radical scavenging, total antioxidant activity, reducing power, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Alpha-hederin, hederasaponin-C, as well as hederacolchisides-E and -F exhibited a strong total antioxidant activity. At the concentration of 75 pg/mL, these saponins showed 94, 86, 88 and 75% inhibition on lipid peroxidation of linoleic acid emulsion,respectively.
CONCLUSIONS:
These various antioxidant activities were compared with model antioxidants such as a-tocopherol, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). | | Planta Med. 2000 May;66(4):343-7. | | Antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro.[Pubmed: 10865451] | The in vitro antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, was investigated on Leishmania infantum.
METHODS AND RESULTS:
The assessment of possible targets (membrane integrity, membrane potential, DNA synthesis and protein content) was performed in both Leishmania promastigotes and human monocytes (THP1 cells). Results observed in Leishmania showed that the saponins exhibited a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential: hederacolchiside A1 appeared to be the most active compound against both promastigotes and amastigotes.
CONCLUSIONS:
Results observed in THP1 cells demonstrated that the saponins exerted also a potent antiproliferative activity against human monocytes, by producing a significant DNA synthesis inhibition. The ratio between antileishmanial activity on amastigotes and toxicity to human cells suggested that the saponins could be considered as possible antileishmanial drugs. | | Phytother Res . 2020 Mar;34(3):601-611. | | α-Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway[Pubmed: 31777126] | | Abstract
α-Hederin, a monodesmosidic triterpenoid saponin, exhibited promising antitumor potential against a variety of human cancer cell lines. However, few related studies about effects of α-hederin on gastric cancer are available. Herein, our results showed that α-hederin significantly inhibited the proliferation of gastric cancer cells and arrested the cell cycle in G1 phase in vitro (p < .05). Further research of the potential mechanism reflected that α-hederin could induce intracellular glutathione decrement, adenosine triphosphate level, and mitochondrial membrane potential variation via inducing reactive oxygen species accumulation during the apoptosis of gastric cancer cells. Moreover, the detection of mitochondrial and cytosol proteins with apoptosis-inducing factor, apoptosis protease activating factor-1, and cytochrome C showed an increase in the cytosol, followed by a decrease of Bcl-2 levels and increases of caspase-3, caspase-8, caspase-9, and Bax, which revealed that α-hederin induced apoptosis via triggering activation of the mitochondrial pathway. Furthermore, the above changes were amplified when pretreated with buthionine sulfoximine, whereas attenuated in the group pretreated with NAC than α-hederin alone (p < .05). In addition, α-hederin significantly inhibited the growth of xenografted gastric tumors with favorable safety. In conclusion, α-hederin could inhibit the proliferation and induce apoptosis of gastric cancer accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway.
Keywords: apoptosis; gastric cancer; glutathione (GSH); mitochondria; reactive oxygen species (ROS); α-hederin. |
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