Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation

Lee, Wonhee; Choi, Joon-Seok; Kim, Ho; Park, Jeong-Hill; Park, Byoung Duck; Cho, Seung Ju; Lee, Seung-Ki; Surh, Young‐Joon

doi:10.1016/j.canlet.2010.01.024

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…KG-135 is a quality-controlled standardized formulation enriched with the red ginseng-specific antitumorigenic ginsenosides such as Rk1, Rg3, and Rg5 [11]. It had been shown to induce marked G1 cell cycle arrest in prostate and cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The quality-controlled standardized ginsenoside formulation KG-135 was prepared as described previously [11] and supplied from the Ginseng Science Inc. (Seoul, Korea). It was dissolved in dimethylsulfoxide (Sigma, St. Louis, MO, USA) and diluted in sterile culture medium immediately prior to use.…”

Section: Methodsmentioning

confidence: 99%

“…This standardized ginsenoside-rich fraction, KG-135, has been shown to inhibit 12-O-tetradecanoylphorbol-13-acetate-induced cyclooxygenase-2 expression in human breast epithelial cells by blocking the c-Jun N-terminal kinase/activator protein-1 signaling pathway [10], suppressing the proliferation of human prostate cancer cells both in vitro and in vivo [8], downregulating G1 cyclin-dependent kinase through the proteasome-mediated pathway [5], and potentiating etoposide-induced apoptosis in human cervical cancer cells [11]. The anticancer effects shown in previous studies of KG-135 are substantial and effective; however, the extent of apoptosis induction by KG-135 in cancer cells seems limited.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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show abstract

“…In another study, KG-135 diminished the proliferative ability of human prostate cancer (DU-145 and PC3) cells and reduced the growth of PC3 cell tumor xenografts in nude mice by inducing cell cycle arrest through the downregulation of cyclin D1 and Cdk expression (101). Moreover, KG-135 has been shown to enhance etoposide-induced apoptosis in HeLa cells by activating p53 and inducing the expression of Bax and p21 (102). These findings indicate that there is ample scope to develop novel ginsenoside formulations by mixing different types of ginsenosides.…”

Section: Future Perspectivesmentioning

confidence: 96%

Biochemical basis of cancer chemoprevention and/or chemotherapy with ginsenosides (Review)

Choi

Chun

Kundu

2013

International Journal of Molecular Medicine

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Cancer still imposes a global threat to public health. After decades of research on cancer biology and enormous efforts in developing anticancer therapies, we now understand that the majority of cancers can be prevented. Bioactive phytochemicals present in edible plants have been shown to reduce the risk of various types of cancer. Ginseng (Panax ginseng C.A. Meyer), which contains a wide variety of saponins, known as ginsenosides, is an age-old remedy for human ailments, including cancer. Numerous laboratory-based studies have revealed the anticancer properties of ginsenosides, which compel tumor cells to commit suicide, arrest the proliferation of cancer cells in culture and inhibit experimentally-induced tumor formation in laboratory animals. Ginsenosides have been reported to inhibit tumor angiogenesis, as well as the invasion and metastasis of various types of cancer cells. Moreover, ginsenosides as combination therapy enhance the sensitivity of chemoresistant tumors to clinically used chemotherapeutic agents. This review sheds light on the molecular mechanisms underlying the cancer chemopreventive and/or chemotherapeutic activity of ginsenosides and their intestinal metabolites with particular focus on the modulation of cell signaling pathways associated with oxidative stress, inflammation, cell proliferation, apoptosis, angiogenesis and the metastasis of cancer cells.

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“…Up-to-now the most promising of these compounds is combretastatin A-4 (cis-3,4,4',5tetramethoxy-3'-hydroxy stilbene ) which has been shown to cause mitotic arrest in a variety of cancer cell lines, including multi-drug-resistant ones, and has also demonstrated cancer antiangiogenetic properties. [52] Panax ginseng…”

Section: Scutellaria Baicalensismentioning

confidence: 99%

Therapeutic Plants of Ayurveda; A Review on Anticancer

Kumar¹,

Jawaid²,

Dubey³

2011

Pharmacognosy Journal

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phytomedicines has increased dramatically in the last two decades. A National Centre for Complementary and Alteranative Medicine has been established in USA. The herbal products have been classified under 'dietary supplements' and are included with vitamins, minerals, amino acids and 'other products intended to supplement the diet'. Use of plants as a medicinal remedy is an integral part of the South African cultural life. It is estimated that 27 million South Africans use herbal medicines from more than 1020 plant species. In fact, there are several medicinal plants all over the World, including India, which are being used traditionally For the prevention and treatment of cancer. Alstonia scholaris Alstonia scholaris, commonly known as sapthaparna, has been used for centuries in Ayurvedic medicine for treatment of various disorders. The objective of this study was to investigate the possible chemopreventive and anti-oxidative properties of this medicinal plant on two-stage process of skin carcinogenesis induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 lg/100 ll acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks) in Swiss albino mice. The tumor incidence, tumor yield, tumor burden and cumulative number

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Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation

Cited by 16 publications

References 22 publications

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

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

Biochemical basis of cancer chemoprevention and/or chemotherapy with ginsenosides (Review)

Therapeutic Plants of Ayurveda; A Review on Anticancer

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