c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

Su, Min‐Xia; Xu, Yan; Jiang, Xiaoming; Huang, Mu‐Yang; Zhang, Le‐Le; Yuan, Luo‐Wei; Xu, Xiao‐Huang; Zhu, Qi; Gao, Jian‐Li; Lu, Jiahong; Chen, Xiuping; Huang, Mingqing; Wang, Ying

doi:10.1016/j.apsb.2021.09.014

Cited by 6 publications

(4 citation statements)

References 63 publications

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“…We have also highlighted in this review the various natural compounds that can induce paraptosis, their different modulators, including the markers that are upregulated during the process (e.g., Bip, CHOP, LC3B, p62), the role of profuse ion channels (potassium and calcium channels, BKCa, IP3R), inhibitors like Alix, PEBP-1. The field’s growth is very evident from the literature that shows the manifold application of paraptosis, counting their role in inducing cell death as a result of treatment with nanomedicines ( Zhou et al, 2018 ), metal complexes ( Tardito et al, 2009 ) or photodynamic therapy ( Kessel and Reiners, 2020 ) and their use in combinatorial treatment approaches ( Su et al, 2022 ). Some of the important milestones of paraptosis research are shown in the timeline in Figure 7 .…”

Section: Discussionmentioning

confidence: 99%

“…mTOR inhibition by everolimus could induce caspase-independent cell death in acute lymphoblastic leukaemia cells ( Baraz et al, 2014 ). A combination of mTOR inhibitor everolimus and ginsenoside Rh2 could trigger cytoplasmic vacuolation-mediated paraptosis ( Su et al, 2022 ). The pro-apoptotic and pro-paraptotic activity of an mTOR inhibitor is elevated upon its combination with Jolkinolide B (JB) through the suppression of AKT feedback activation and cytoprotective autophagy ( Sang et al, 2022 ).…”

Section: Recent Trends In Paraptosis Researchmentioning

confidence: 99%

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Paraptosis: a unique cell death mode for targeting cancer

Hanson,

Dharan,

P. V.

et al. 2023

Front. Pharmacol.

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Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems’ development, health and disease. Out of all, apoptosis is one of the major PCDs that was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire the ability to escape apoptotic cell death, thereby increasing their resistance towards current therapies. This issue has led to the need to search for alternate forms of programmed cell death mechanisms. Paraptosis is an alternative cell death pathway characterized by vacuolation and damage to the endoplasmic reticulum and mitochondria. Many natural compounds and metallic complexes have been reported to induce paraptosis in cancer cell lines. Since the morphological and biochemical features of paraptosis are much different from apoptosis and other alternate PCDs, it is crucial to understand the different modulators governing it. In this review, we have highlighted the factors that trigger paraptosis and the role of specific modulators in mediating this alternative cell death pathway. Recent findings include the role of paraptosis in inducing anti-tumour T-cell immunity and other immunogenic responses against cancer. A significant role played by paraptosis in cancer has also scaled its importance in knowing its mechanism. The study of paraptosis in xenograft mice, zebrafish model, 3D cultures, and novel paraptosis-based prognostic model for low-grade glioma patients have led to the broad aspect and its potential involvement in the field of cancer therapy. The co-occurrence of different modes of cell death with photodynamic therapy and other combinatorial treatments in the tumour microenvironment are also summarized here. Finally, the growth, challenges, and future perspectives of paraptosis research in cancer are discussed in this review. Understanding this unique PCD pathway would help to develop potential therapy and combat chemo-resistance in various cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Recent Trends In Paraptosis Researchmentioning

confidence: 99%

Paraptosis: a unique cell death mode for targeting cancer

Hanson,

Dharan,

P. V.

et al. 2023

Front. Pharmacol.

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“…Furthermore, in our study the content of minor ginsenoside Rh 2 in the SLPN-instant beverage was 1.64 ± 0.14 mg/g-DW, being five times higher than that in SLPN. G-Rh 2 could inhibit colorectal cancer cell growth ( 56 ), suppress the proliferation of A549 cells ( 57 ), breast cancer cell growth ( 58 ), and moreover the combination of G-Rh 2 could induce lung cancer ( 59 ). Up to date, G-Rh 2 is being developed as a new antitumor drug.…”

Section: Discussionmentioning

confidence: 99%

An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng

Liang

Liu²,

Li³

et al. 2022

Front. Nutr.

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IntroductionRadix Notoginseng, one of the most famous Chinese traditional medicines, is the dried root of Panax notoginseng (Araliaceae). Stems and leaves of P. notoginseng (SLPN) are rich in secondary metabolites and nutrients, and authorized as a food resource, however, its utilization needs further research.MethodsA SLPN-instant beverage was manufactured from SLPN through optimization by response surface design with 21-fold of 48.50% ethanol for 39 h, and this extraction was repeated twice; the extraction solution was concentrated to 1/3 volume using a vacuum rotatory evaporator at 45°C, and then spray dried at 110°C. Nutritional components including 14 amino acids, ten mineral elements, 15 vitamins were detected in the SLPN-instant beverage; forty-three triterpenoid saponins, e.g., ginsenoside La, ginsenoside Rb3, notoginsenoside R1, and two flavonoid glycosides, as well as dencichine were identified by UPLC-MS.ResultsThe extraction rate of SLPN-instant beverage was 37.89 ± 0.02%. The majority nutrients were Gly (2.10 ± 0.63 mg/g), His (1.23 ± 0.07 mg/g), α-VE (18.89 ± 1.87 μg/g), β-VE (17.53 ± 1.98 μg/g), potassium (49.26 ± 2.70 mg/g), calcium (6.73 ± 0.27 mg/g). The total saponin of the SLPN-instant beverage was 403.05 ± 34.98 mg/g, majority was notoginsenoside Fd and with contents of 227 ± 2.02 mg/g. In addition, catechin and γ-aminobutyric acid were detected with levels of 24.57 ± 0.21 mg/g and 7.50 ± 1.85 mg/g, respectively. The SLPN-instant beverage showed good antioxidant activities with half maximal inhibitory concentration (IC50) for scavenging hydroxyl (OH–) radicals, superoxide anion (O2–) radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS+) radicals were 0.1954, 0.2314, 0.4083, and 0.3874 mg/mL, respectively.ConclusionWe optimized an analytical method for in depth analysis of the newly authorized food resource SLPN. Together, an instant beverage with antioxidant activity, rich in nutrients and secondary metabolites, was manufactured from SLPN, which may improve the utilization of SLPN.

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“…In addition, studies have shown that combined with everolimus, Rh2 attenuates everolimus-induced hepatic steatosis and induces parapoptosis, thereby enhancing anti-cancer activity. 130 Parapoptosis is a new type of programmed cell death involving cytoplasmic vacuolization, and many natural products such as paclitaxel, proanthocyanidins, curcumin and ginsenosides are now available to induce this process and play an important role in cancer therapy and overcoming drug resistance. 134 Moreover, abnormal lipid metabolism is one of the hallmarks of cancer, and reprogramming of lipid metabolism is a mechanism of drug resistance.…”

Section: Inhibition Of Drug Resistance and Enhancement Of Chemosensit...mentioning

confidence: 99%

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease

Wang,

Zhang,

Song

et al. 2023

Food Funct.

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c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

Cited by 6 publications

References 63 publications

Paraptosis: a unique cell death mode for targeting cancer

Paraptosis: a unique cell death mode for targeting cancer

An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease

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