Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway

Wang, Lei; Li, Xiankui; Song, Yimin; Wang, Bin; Zhang, Fu‐Rui; Yang, Rui; Wang, Hua‐qi; Zhang, Guojun

doi:10.3892/mmr.2015.3397

Cited by 44 publications

(30 citation statements)

References 26 publications

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“…Activated NF‐κB eventually binds to κB elements in the promoter region of target genes and initiates the transcriptional process of numerous genes . Recent investigations have demonstrated that the NF‐κB pathway is suppressed by a large number of ginsenosides, including Rg1, Rh2, Rb1, Compound K (CK), Rg3, Rb3, Rd, Pseudoginsenoside‐F11 (PF11), Re, Rh1, Rf, 20( S )‐protopanaxatriol, and Ro (Fig. ).…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

“…Moreover, Rh1 blocked the invasion and migration of human astroglioma cells ; (2) the enhancement of cancer cell sensitivity by ginsenosides has also been documented. Rg3 sensitized nonsmall cell lung cancer (NSCLC) to γ ‐radiation and 20( S )‐Rh2 improved the cellular pharmacokinetic behaviors and cytotoxicity of Adriamycin in Adriamycin‐resistant MCF‐7 cells; and (3) ginsenosides also directly inhibited the growth of human cancer. For example, Rg3 induced apoptosis and suppressed the growth of human melanoma cancer …”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

“…43 Under physiological conditions, NF- and initiates the transcriptional process of numerous genes. 44,45 Recent investigations have demonstrated that the NF-B pathway is suppressed by a large number of ginsenosides, including Rg1, [46][47][48][49][50][51][52][53][54][55][56][57] Rh2, [58][59][60][61] Rb1, [62][63][64] Compound K (CK), 65,66 Rg3, [67][68][69][70][71][72] Rb3, 73 Rd, [74][75][76] Pseudoginsenoside-F11 (PF11), 77 Re, 78 Rh1, 79 Rf, 80 20(S)-protopanaxatriol, 52 and Ro 81,82 ( Fig. 3).…”

Section: Nf-b Pathway and The Effect Of Ginsenosidesmentioning

confidence: 99%

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Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

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Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

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Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

Section: Nf-b Pathway and The Effect Of Ginsenosidesmentioning

confidence: 99%

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Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

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“…This may be a key mechanism behind the preventive effects of these 4 injections on RILI [36]. Ginsenoside Rg3 a main ingredient of ginseng extractions was able to sensitize A549 and H1299 lung carcinoma cells to γ -radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor [52]. Radix Astragali in SQFZI and YZXJC is considered as potential and powerful exogenous source of antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Chinese Herbal Extractions for Relieving Radiation Induced Lung Injury: A Systematic Review and Meta‐Analysis

Deng

Cheng

2017

Evidence-Based Complementary and Alternative Medicine

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Background. Radiation induced lung injury (RILI) is one of the most common and severe side effects of thoracic radiotherapy. In this meta-analysis, the effects of Chinese herbal extractions (CHE) for preventing and treating RILI are evaluated. Methods. Randomized Controlled Trials (RCTs) from five databases were identified. Studies were evaluated and the relevant data were extracted by two authors independently. Differences were resolved by a third party. Meta-analysis was conducted using RevMan 5.0. Results. In total, 2734 participants receiving thoracic radiotherapy were included in 28 RCTs, and 16 CHE were evaluated. Meta-analysis showed that CHE intervention significantly reduced the incidence of acute radiation pneumonitis (RP) and radiation induced pulmonary fibrosis (RIPF). In CHE group, total effective rate and remission rate of RILI patients were significantly higher. Patient's quality of life (Qol) and clinical symptoms and signs were improved significantly. Inflammatory cytokines decreased, and thymus dependent lymphocytes subgroups were improved. Conclusion. CHE intervention may have clinical effectiveness for relieving RILI and related symptoms and signs and lead to improvement of Qol. However, more double-blind, multicenter, large-scale RCTs are needed to support this theory. Trial Registration. PROSPERO International prospective register of systematic reviews has registration number CRD42016043538.

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“…New approaches are needed to tackle this disease. As such, natural phytochemicals like ginsenosides or their derivatives have being studied for their potential in NSCLC treatment [25], [26], [27], [28], [29], [30].…”

Section: Introductionmentioning

confidence: 99%

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Yao

Chow

Chuang

et al. 2017

Journal of Ginseng Research

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BackgroundKG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy.MethodsCell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange.ResultsKG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis.ConclusionBesides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

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Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway

Cited by 44 publications

References 26 publications

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Chinese Herbal Extractions for Relieving Radiation Induced Lung Injury: A Systematic Review and Meta‐Analysis

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

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