Balanitin-6 and -7: Diosgenyl saponins isolated from Balanites aegyptiaca Del. display significant anti-tumor activity in vitro and in vivo

Gnoula, Charlemagne; Mégalizzi, Veronique; Nève, Nancy De; Sauvage, Sébastien; Ribaucour, Fabrice; Guissou, Pierre I.; Duez, Pierre; Dubois, Jacques; Ingrassia, Laurent; Lefranc, Florence; Kiss, Róbert; Mijatovic, Tatjana

doi:10.3892/ijo.32.1.5

Cited by 46 publications

(58 citation statements)

References 38 publications

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“…Bal6/7 demonstrated IC 50 in vitro growth inhibitory concentrations in U373 GBM and A549 NSCLC cells quite similar for those observed here for ISP, i.e., 0.3 μM (Bal6/7) versus 0.8 μM (ISP) in A549 NSCLC cells and 0.5 μM (Bal6/7) versus 0.8 μM (ISP) in U373 GBM cells (30). Bal6/7 exerts its anti-cancer effects without inducing apoptotic cell death (30), but its in vitro anti-cancer activities result at least partly from depletion of [ATP] i , leading in turn to major disorganization of actin cytoskeleton, ultimately resulting in the impairment of cancer cell proliferation (at the level of cytokinesis) and migration (30). In contrast to a number of natural products acting as anti-cancer agents, bal6/7 does not induce an increase in intra-cellular reactive oxygen species (30).…”

Section: Discussionsupporting

confidence: 63%

“…Bal6/7 exerts its anti-cancer effects without inducing apoptotic cell death (30), but its in vitro anti-cancer activities result at least partly from depletion of [ATP] i , leading in turn to major disorganization of actin cytoskeleton, ultimately resulting in the impairment of cancer cell proliferation (at the level of cytokinesis) and migration (30). In contrast to a number of natural products acting as anti-cancer agents, bal6/7 does not induce an increase in intra-cellular reactive oxygen species (30). In the present study, while we observed transient ISP-induced decreases in [ATP] i in U373 GBM cells, a feature that could explain (at least partly) ISP-induced proapoptotic effects in these U373 cells, we did not observe ISP-induced decrease in [ATP] i nor induction of apoptosis in A549 NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The balanitin-6 and -7 mixture (henceforth referred to as bal6/7) has demonstrated appreciable anti-cancer effects in human cancer cell lines in vitro (30). Bal6/7 demonstrated IC 50 in vitro growth inhibitory concentrations in U373 GBM and A549 NSCLC cells quite similar for those observed here for ISP, i.e., 0.3 μM (Bal6/7) versus 0.8 μM (ISP) in A549 NSCLC cells and 0.5 μM (Bal6/7) versus 0.8 μM (ISP) in U373 GBM cells (30). Bal6/7 exerts its anti-cancer effects without inducing apoptotic cell death (30), but its in vitro anti-cancer activities result at least partly from depletion of [ATP] i , leading in turn to major disorganization of actin cytoskeleton, ultimately resulting in the impairment of cancer cell proliferation (at the level of cytokinesis) and migration (30).…”

Section: Discussionmentioning

confidence: 99%

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Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Baldé

Mégalizzi²,

Cao³

et al. 2010

Int J Oncol

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Abstract. Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, an East African small tree. We have reported previously pro-apoptotic effects induced in vitro by ISP in the human HCT-116 colon cancer cell line, a model that displays relative sensitivity to apoptosis. In the present study, we observed that the in vitro growth inhibitory activities of ISP are similar in cancer cells that display sensitivity versus resistance to apoptosis. We made use of the U373 glioblastoma and the A549 non-small cell lung cancer (NSCLC) cell lines as models relatively resistant to apoptosis, and the human PC-3 prostate cancer cell line as a model relatively sensitive to apoptosis. While ISP induced transient decreases in [ATP] i and apoptosis in human U373 GBM cells, it did not provoke such features in A549 NSCLC cells. It thus seems that ISPinduced anti-cancer activity can lead to pro-apoptotic effects as a consequence, while apoptosis seems not to be the main cause by which ISP induces cancer cell death. ISP is a compound that merits further investigations in order to: i) identify the mechanism(s) of action by which it kills cancer cells, and ii) hemisynthesize novel ISP derivatives aiming to overcome, at least partly, the resistance of metastatic cancers to apoptosis. IntroductionDespite frequent responses to chemotherapy, curative treatment remains elusive for the majority of patients with metastatic solid tumors (1). Indeed, in the common advanced cancers, over 40 years of cytotoxic drug development has brought no significant change in cure rates (1). Savage and colleagues (1) report that one interpretation is that the intrinsic properties of the malignancies themselves, rather than the qualities of individual drugs or combination therapies, are primarily responsible for their curability with chemotherapy. These authors thus suggest that the curability of these malignancies results from an intrinsic 'locked-in' state of sensitivity to proapoptotic stresses in these cells (1). In fact, >90% of cancer patients die from their metastases (2). Drug resistance, either acquired or intrinsic, often prevents tumor cells from undergoing sufficient levels of apoptosis, resulting in cancer cell survival and treatment failure (1,2). The metastatic process is inherent to a significant level of resistance to apoptosis. Indeed, as a barrier to metastases, cells normally undergo apoptosis after they lose contact with their extra cellular matrix or their neighboring cells (3). This cell death process has been termed 'anoikis' (3). Tumor cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while travelling through the lymphatic and circulatory systems (3). Defects in the death receptor pathway of caspase activation, such as the over-expression of the caspase-8 inhibitor FLIP, can render cells resistant to anoïkis (3).Plants have played a dominant role in the development of sophisticate...

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Baldé

Mégalizzi²,

Cao³

et al. 2010

Int J Oncol

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“…23 Suppressed tumor growth was also observed for other saponins like 51,52 and several other saponins. 52,53,[70][71][72][73][74][75][76][77][78][79] A further prominent feature of saponins is their antimicrobial activity. Diosgenyl 2-amino-2-deoxy-beta-D-glucopyranoside was medically active against Staphylococcus aureus and Enterococcus faecalis in a wound model simulating surgical site infections in BALB/c mice.…”

Section: Efficacy Of Saponins and Clinical Potentialmentioning

confidence: 99%

Chemistry and pharmacology of saponins: special focus on cytotoxic properties

Thakur¹,

Melzig²,

Fuchs³

et al. 2011

BTAT

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Saponins are bioactive compounds produced mainly by plants but also by some marine organisms and insects. In the recent past, there has been unforeseen interest in the clinical utilization of saponins as chemotherapeutic agents. The research on saponins in various forms as a treatment for cancer has generated a lot of potential. The advent of nanotechnology and the cytotoxicity enhancing properties of saponins are some of the highlights of the current decade. This review gives an updated overview of the clinical potential that saponins hold as cytotoxic agents, and covers the literature for 1957-2011, with the main focus on research conducted in the last decade. It is conceivable that saponins hold a lot of therapeutic potential and could be a lead for identification of synthetic or semisynthetic molecules for the treatment of cancer via membrane-mediated or transport-mediated pathways.

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Recent advances in steroidal saponins biosynthesis and in vitro production

Upadhyay

Jeena

Shikha

et al. 2018

Planta

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Main conclusion Steroidal saponins exhibited numerous pharmacological activities due to the modification of their backbone by different cytochrome P450s (P450) and UDP glycosyltransferases (UGTs). Plant-derived steroidal saponins are not sufficient for utilizing them for commercial purpose so in vitro production of saponin by tissue culture, root culture, embryo culture, etc, is necessary for its large-scale production.Saponin glycosides are the important class of plant secondary metabolites, which consists of either steroidal or terpenoidal backbone. Due to the existence of a wide range of medicinal properties, saponin glycosides are pharmacologically very important. This review is focused on important medicinal properties of steroidal saponin, its occurrence, and biosynthesis. In addition to this, some recently identified plants containing steroidal saponins in different parts were summarized. The high throughput transcriptome sequencing approach elaborates our understanding related to the secondary metabolic pathway and its regulation even in the absence of adequate genomic information of non-model plants. The aim of this review is to encapsulate the information related to applications of steroidal saponin and its biosynthetic enzymes specially P450s and UGTs that are involved at later stage modifications of saponin backbone. Lastly, we discussed the in vitro production of steroidal saponin as the plant-based production of saponin is time-consuming and yield a limited amount of saponins. A large amount of plant material has been used to increase the production of steroidal saponin by employing in vitro culture technique, which has received a lot of attention in past two decades and provides a way to conserve medicinal plants as well as to escape them for being endangered.

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Balanitin-6 and -7: Diosgenyl saponins isolated from Balanites aegyptiaca Del. display significant anti-tumor activity in vitro and in vivo

Cited by 46 publications

References 38 publications

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Chemistry and pharmacology of saponins: special focus on cytotoxic properties

Recent advances in steroidal saponins biosynthesis and in vitro production

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