A steroidal saponin form &lt;i&gt;Paris vietnamensis&lt;/i&gt; (Takht.) reverses temozolomide resistance in glioblastoma cells &lt;i&gt;via&lt;/i&gt; inducing apoptosis through ROS/PI3K/Akt pathway

Zhang, Shan; Lu, Yang; Li, Hua; Ji, Yibing; Fang, Fei; Tang, Hai‐Feng; Qiu, Pengcheng

doi:10.5582/bst.2020.01005

Cited by 18 publications

(10 citation statements)

References 36 publications

(38 reference statements)

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“…and suppressed cell proliferation in a dose‐dependent manner in U87, U251, and temozolomide‐resistant U87R glioblastoma cell lines. [ 9 ] Mechanistic studies revealed that N45 could suppress cell proliferation by inducing mitochondrial apoptosis through the reactive oxygen species (ROS)/phosphoinositide 3‐kinase (PI3K)/Akt signaling pathway. In addition, N45 decreased drug resistance by downregulating nuclear factor κ‐B p65 (NF‐κB p65) to attenuate O 6 ‐methylguanine‐DNA methyltransferase in a temozolomide‐resistant U87R glioblastoma cell line.…”

Section: Steroidal Saponinsmentioning

confidence: 99%

Current perspectives on naturally occurring saponins as anticancer agents

Wang

2022

Archiv der Pharmazie

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Saponins, a heterogeneous group of sterol and triterpene glycosides, are distributed widely in nature. Naturally occurring saponins could act on diverse targets in cancer cells and consequently exert potential antiproliferative effects in various cancers, including drug‐resistant forms. Therefore, naturally occurring saponins are useful templates for the discovery of novel anticancer candidates. Covering articles published between January 2020 and October 2021, this review aims to outline the recent development of naturally occurring steroidal and triterpenoidal saponins with anticancer potential to provide novel anticancer lead hits/candidates.

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Section: Steroidal Saponinsmentioning

confidence: 99%

Current perspectives on naturally occurring saponins as anticancer agents

Wang

2022

Archiv der Pharmazie

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“…However, arctigenin, curcumin, diosgenin, and berberine downregulate (p-)mTOR, while diosgenin downregulates NF-κB [ 29 , 54 , 61 ]. Moreover, galbanic acid exerts antiproliferative, anti-metastatic, and pro-apoptotic effects via PI3K/Akt/mTOR signaling, while N45, a natural steroidal saponin, upregulates apoptosis through ROS/PI3K/Akt signaling in TMZ-resistant GBM cells [ 65 , 66 ].…”

Section: Mechanistic Effects Of Natural Compounds On Glioblastomamentioning

confidence: 99%

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Zhai

Siddiqui

Abdellatif

et al. 2021

Cancers

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Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.

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“…This indicated that CN‐3 may lead to mitochondrial apoptosis in SHG44R and U87R cells. [ 42 ] To determine the molecular mechanism underlying CN‐3‐induced apoptosis in glioblastoma cells, a western blot assay was used to evaluate the expression of phosphorylated AKT (p‐AKT), Bax, Bcl‐2, cytochrome C, PARP‐1, and cleaved‐caspase 3 signaling‐pathway‐related proteins. After SHG44R and U87R cells were treated with CN‐3 for 24 h, the expression of Bax, cleaved‐caspase 3, and cytochrome C was significantly increased, whereas that of PARP‐1, P‐AKT, and Bcl‐2 was significantly decreased (Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

“…in U87R cells. [ 42 ] In this study, the reactive oxygen scavenging agent NAC was used, and the results showed that ROS mediated the inhibitory effect of CN‐3 on SHG44R and U87R cells. CCK‐8 detection results showed that 4 mg/ml NAC rescued the inhibitory effect of CN‐3 on SHG44R and U87R cells (Figure 5A).…”

Section: Discussionmentioning

confidence: 99%

“…), which reverses TMZ resistance in glioblastoma cells via induction of apoptosis through the reactive oxygen species (ROS)/PI3K/Akt pathway. [ 42 ] Due to highly diverse marine habitats, metabolites isolated from marine organisms continue to be a rich and valuable source of bioactive natural chemicals. [ 43,44 ] Starfish are one of the most common marine organisms inhabiting a wide range of habitats.…”

Section: Introductionmentioning

confidence: 99%

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CN‐3 increases TMZ sensitivity and induces ROS‐dependent apoptosis and autophagy in TMZ‐resistance glioblastoma

Xue

Sun

et al. 2021

J Biochem & Molecular Tox

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Many glioma patients develop resistance to temozolomide (TMZ) treatment, resulting in reduced efficacy and survival rates. TMZ‐resistant cell lines SHG44R and U87R, which highly express O6‐methylguanine DNA methyltransferase (MGMT) and P‐gp, were established. CN‐3, a new asterosaponin, showed cytotoxic effects on TMZ‐resistant cells in a dose‐ and time‐dependent manner via reactive oxygen species (ROS)‐mediated apoptosis and autophagy. Transmission electron microscopy and monodansylcadaverine (MDC) staining showed turgidity of the mitochondria and autophagosomes in CN‐3‐treated SHG44R and U87R cells. The autophagy inhibitor 3‐methyladenine was used to confirm the important role of autophagy in CN‐3 cytotoxicity in TMZ‐resistant cells. The ROS scavenger N‐acetyl‐ l‐cysteine (NAC) attenuated the levels of ROS induced by CN‐3 and, therefore, rescued the CN‐3 cytotoxic effect on the viability of SHG44R and U87R cells by Cell Counting Kit‐8 assays and JuLI‐Stage videos. MDC staining also confirmed that NAC rescued an autophagosome increase in CN‐3‐treated SHG44R and U87R cells. Western blotting revealed that CN‐3 increased Bax, cleaved‐caspase 3, cytochrome C, PARP‐1, LC3‐Ⅱ, and Beclin1, and decreased P‐AKT, Bcl‐2, and p62. Further rescue experiments revealed that CN‐3 induced apoptosis and autophagy through ROS‐mediated cytochrome C, cleaved‐caspase 3, Bcl‐2, P‐AKT, PARP‐1, and LC3‐Ⅱ. In addition, CN‐3 promoted SHG44R and U87R cells sensitive to TMZ by reducing the expression of P‐gp, MGMT, and nuclear factor kappa B p65, and it had a synergistic cytotoxic effect with TMZ. Moreover, CN‐3 disrupted the natural cycle arrest and inhibited the migration of SHG44R and U87R cells by promoting cyclin E1 and D1, and by decreasing P21, P27, N‐cadherin, β‐catenin, transforming growth factor beta 1, and Smad2.

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A steroidal saponin form <i>Paris vietnamensis</i> (Takht.) reverses temozolomide resistance in glioblastoma cells <i>via</i> inducing apoptosis through ROS/PI3K/Akt pathway

Cited by 18 publications

References 36 publications

Current perspectives on naturally occurring saponins as anticancer agents

Current perspectives on naturally occurring saponins as anticancer agents

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

CN‐3 increases TMZ sensitivity and induces ROS‐dependent apoptosis and autophagy in TMZ‐resistance glioblastoma

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