The anti-tumor activity of Antrodia salmonea in human promyelocytic leukemia (HL-60) cells is mediated via the induction of G1 cell-cycle arrest and apoptosis in vitro or in vivo

Hseu, You‐Cheng; Lee, Chuan-Chen; Chen, Yung‐Chang; Kumar, K. J. Senthil; Chen, Chee‐Shan; Huang, Yuchi; Hsu, Li‐Sung; Huang, Hui‐Chi; Yang, Hsin‐Ling

doi:10.1016/j.jep.2014.03.012

Cited by 28 publications

(25 citation statements)

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“…Excess ROS generation has been well-characterized to cause damage to the mitochondrial membrane, and the damaged mitochondria may lead to cell death (19,20). Therefore, it was examined whether KQ-induced ROS generation could trigger mitochondrial membrane damage in HeLa cells.…”

Section: Kq Stimulates Loss Of δψ M In Hela Cellsmentioning

confidence: 99%

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericumï¿½ascyron L.

Luo

et al. 2018

Oncol Lett

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Abstract. Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed. The results demonstrated that the anti-proliferative action of the mixture of kaempferol 3-O-β-(2"-acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti-proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti-proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs. IntroductionInvasive cervical cancer is one of the most common forms of female malignancies worldwide (1). According to an estimate, in 2008 alone there were ~530,000 novel cases of invasive cervical cancer and ~275,000 cervical cancer-associated mortalities worldwide (1,2). A growing number of young patients suffer from cervical cancer and the pathological types of the malignancies undergo changes (2). Current treatments for cervical cancer include surgery, radiation and chemotherapy, and conventional chemotherapy remains the most common treatment for advanced-stage cancers (3). In the last decade, increasing advances in cancer research have enhanced the understanding of cancer biology and genetics, and anticancer effects may be exhibited through selective cytotoxicity, anti-proliferative action, stimulation of apoptosis and induction of differentiation (4,5).Hypericum ascyron L. (Great St. Johnswort) has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China (6,7). H. ascyron L. extract has been investigated and revealed to exhibit anticancer activities (8,9). H. ascyron L. extract also possesses numerous other beneficial functions, including inhibition of histamine release (10), anti-inflammatory activity, analgesic effects (11), antioxidant activity (11),...

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Section: Kq Stimulates Loss Of δψ M In Hela Cellsmentioning

confidence: 99%

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericumï¿½ascyron L.

Luo

et al. 2018

Oncol Lett

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“…Potent cytotoxicity of coenzyme Q 0 towards triple negative breast cancer cells (TNBCs), induction of apoptosis, and modulation of the cell cycle have been reported in another study (Somers‐Edgar & Rosengren, ). In addition, our previous study showed the HPLC chemical profile of A. salmonea was determined using an RP‐18 column and detected at a UV wavelength of 280 nm (Hseu et al, ). The compound 2,4‐dimethoxy‐6‐methylbenzene‐1, 3‐diol (11.6%) in A. salmonea was detected at retention time of 15.1 min (Chang, Korivi, et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The lyophilized sample were ground, shaken with distilled water, and centrifuged at 3000g for 5 min, taken after and filtered through a 0.22-μm filter. The aqueous extracts were concentrated in a vacuum freeze dryer to form a powder (Chang, Korivi, et al, 2017;Hseu et al, 2014). The yield of the fermented culture broth of 1 g of A.…”

Section: Preparation Of a Salmonea Submerged Culturesmentioning

confidence: 99%

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Antrodia salmonea‐induced oxidative stress abrogates HER‐2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells

Yang

Lin

Rajendran

et al. 2018

Journal Cellular Physiology

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Antrodia salmonea is well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti-inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV-3 or A2780) cell lines with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells and annexin V-propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV-3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase-3, -8, -9 and poly(ADP-ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2-B-cell lymphoma 2 dysregulation. The results show that A. salmonea-induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented A. salmonea-induced cell death and DNA fragmentation, indicating that A. salmonea-induced apoptosis was mediated by ROS generation. Interestingly, A. salmonea-induced apoptosis is associated with the suppression of human epidermal growth factor receptor-2 (HER-2/neu) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) expression in HER-2/neu overexpressing SKOV-3 cells. NAC significantly prevented A. salmonea-induced HER-2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea-triggered apoptosis is mediated by ROS-inhibited HER-2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma.

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“…In Taiwanese folk medicine, the fruit of A. salmonea is utilized in the treatment of abdominal pain, cancer, diarrhea, hypertension, drug intoxication, and itchy skin (Shen et al, 2008). Recent reports from our laboratory have shown that crude extracts of A. salmonea have the potential to exert antioxidant, anti-inflammatory, and antitumor activities (Chang, Hseu, et al, 2017;Chang, Korivi, et al, 2017;Hseu et al, 2014aHseu et al, , 2014bHuang, Pan, Liu, Wu, & Wu, 2012). Our previous study showed that A. salmonea causes ROS-mediated apoptosis in human ovarian carcinoma cells (H. L. Yang et al, 2018).…”

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confidence: 99%

Induction of autophagic cell death in human ovarian carcinoma cells by Antrodia salmonea through increased reactive oxygen species generation

Yang

Lin

Karuppaiya

et al. 2018

Journal Cellular Physiology

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We reported in our previously executed studies that the fermented culture broth of Antrodia salmonea (AS), a mushroom used in Taiwanese folk medicine induced reactive oxygen species (ROS)‐mediated apoptosis in human ovarian carcinoma cells. In this study, we studied the anticancer efficacies of AS (0–240 μg/ml) by examining the key molecular events implicated in cell death associated with autophagy in SKOV‐3 and A2780 human ovarian carcinoma cells and clarified the fundamental molecular mechanisms. Treatment of ovarian carcinoma cells with AS‐induced autophagic cell death mediated by increased microtubule‐associated protein LC3‐II, GFP‐LC3 puncta, and acidic vesicular organelle (AVO) formation. These events are linked with the activation of p62/SQSTM1, the inhibition of ATG4B, the expression of ATG7, and the dysregulation of Beclin‐1/Bcl‐2 (i.e., B‐cell lymphoma 2). N‐acetylcysteine inhibited AS‐induced ROS generation, which in turn constricted AS‐induced LC3 conversion, AVO formation, and ATG4B inhibition, indicating ROS‐mediated autophagy cell death. In addition, the 3‐methyladenine (3‐MA) or chloroquine (CQ)‐induced autophagy inhibition decreased AS‐induced apoptosis. Additionally, apoptosis inhibition by Z‐VAD‐FMK, a pan‐caspase inhibitor, substantially suppressed AS‐induced autophagy. Furthermore, AS‐inhibited HER‐2/ neu and PI3K/AKT signaling pathways which were reversed by autophagy inhibitors 3‐MA and CQ. Thus, A. salmonea is a potential chemopreventive agent that is capable of activating ROS‐mediated autophagic cell death in ovarian carcinoma cells.

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The anti-tumor activity of Antrodia salmonea in human promyelocytic leukemia (HL-60) cells is mediated via the induction of G1 cell-cycle arrest and apoptosis in vitro or in vivo

Cited by 28 publications

References 35 publications

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericumï¿½ascyron L.

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericumï¿½ascyron L.

Antrodia salmonea‐induced oxidative stress abrogates HER‐2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells

Induction of autophagic cell death in human ovarian carcinoma cells by Antrodia salmonea through increased reactive oxygen species generation

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