Cytotoxicity of a naturally occuring spirostanol saponin, progenin III, towards a broad range of cancer cell lines by induction of apoptosis, autophagy and necroptosis

Mbaveng, Armelle T.; Fru, Godloves; Nguenang, Gaëlle S.; Abdelfatah, Sara; Sop, Rodrigue V. Tchangna; Ngadjui, Bonaventure T.; Kuete, Victor; Efferth, Thomas

doi:10.1016/j.cbi.2020.109141

Cited by 40 publications

(23 citation statements)

References 45 publications

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“…Furthermore, Gao et al discovered a novel form of cell death in tumor cells in which exposure to trisaccharide saponin derivatives induced cell swelling followed by cell membrane perturbation and destruction of the cytoskeletal network in the form of cell death known as oncotic necrosis [ 88 ]. Polyphyllin D and progenin III can induce programmed necrosis/necroptosis in cancer cells [ 26 , 89 , 90 ]. The molecular mechanism by which saponins exert necroptosis is not fully known, but similar to apoptotic cell death, it involves the activation of Caspase 8 as observed in the extrinsic pathway of apoptosis [ 26 ].…”

Section: Anticancer Mechanisms Of Saponinmentioning

confidence: 99%

Saponins in Cancer Treatment: Current Progress and Future Prospects

et al. 2021

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Saponins are steroidal or triterpenoid glycoside that is distinguished by the soap-forming nature. Different saponins have been characterized and purified and are gaining attention in cancer chemotherapy. Saponins possess high structural diversity, which is linked to the anticancer activities. Several studies have reported the role of saponins in cancer and the mechanism of actions, including cell-cycle arrest, antioxidant activity, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effects of saponins, there are currently no known FDA-approved saponin-based anticancer drugs. This can be attributed to a number of limitations, including toxicities and drug-likeness properties. Recent studies have explored options such as combination therapy and drug delivery systems to ensure increased efficacy and decreased toxicity in saponin. This review discusses the current knowledge on different saponins, their anticancer activity and mechanisms of action, as well as promising research within the last two decades and recommendations for future studies.

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Section: Anticancer Mechanisms Of Saponinmentioning

confidence: 99%

Saponins in Cancer Treatment: Current Progress and Future Prospects

et al. 2021

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“… a CEM, cells of human T-lymphoblastic leukemia; b MCF7, cells of human breast adenocarcinoma; c HeLa, cells of human cervical cancer; d HCT 116, human colon carcinoma; e BJ, normal human fibroblasts; f NT = not tested in our team; however, IC 50 value (CEM) 0.02 + 0.00 µM (ref. [ 26 ]). …”

Section: Figure Scheme and Tablesmentioning

confidence: 99%

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

et al. 2020

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The target diosgenin–betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.

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“…Integrating the sterol 3-O-glucosyltransferase gene and DzGT1 into the diosgenin-producing yeasts, PSA is most likely synthesized. Pharmacological studies show that PSA has antiplatelet aggregation and anti-cancer activities (Wang et al, 2014;Mbaveng et al, 2020), and it can be developed as a new drug in the future. However, the biosynthetic pathway of the sugar chain of dioscin has not been elucidated completely.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Trillin Rhamnosyltransferase From Dioscorea zingiberensis

Mosongo

Han

et al. 2021

Front. Plant Sci.

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Dioscorea zingiberensis accumulates abundant steroidal saponins, such as dioscin, which is the principal bioactive ingredient displaying a wide range of pharmacological activities. Diosgenin is the aglycone of dioscin, and recently, genes encoding cytochrome P450 enzymes in the late steps of diosgenin biosynthesis have been isolated. Diosgenin was successfully synthesized in the cholesterol-producing yeasts. From diosgenin to dioscin, one glucose and two rhamnose groups need to be added. Although genes encoding UDP-glucosyltransferases converting diosgenin to trillin were isolated, genes encoding UDP-rhamnosyltransferases involved in dioscin biosynthesis remain unknown. In this study, we isolated the cDNA encoding the trillin rhamnosyltransferase (designated DzGT1) from D. zingiberensis. Heterologous expression of DzGT1 in Escherichia coli cells showed that the gene product exhibits an enzyme activity that glycosylates the trillin to form prosapogenin A of dioscin (PSA). The transcript level of DzGT1 is in accord with PSA accumulation in different organs of D. zingiberensis. Integration of the biochemical, metabolic, and transcriptional data supported the function of DzGT1 in dioscin biosynthesis. The identification and characterization of DzGT1 will help understand the metabolism of steroidal saponins in D. zingiberensis and provide candidate UDP-rhamnosyltransferase for efficient production of PSA, dioscin, and relevant steroidal saponins in microbial hosts.

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Cytotoxicity of a naturally occuring spirostanol saponin, progenin III, towards a broad range of cancer cell lines by induction of apoptosis, autophagy and necroptosis

Cited by 40 publications

References 45 publications

Saponins in Cancer Treatment: Current Progress and Future Prospects

Saponins in Cancer Treatment: Current Progress and Future Prospects

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

Identification and Characterization of a Trillin Rhamnosyltransferase From Dioscorea zingiberensis

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