Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production

Shen, Shin-Yu

doi:10.1016/s0041-008x(04)00106-1

Cited by 20 publications

(24 citation statements)

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“…Flavonoids, the major component of natural products derived from plants, behave as an antioxidant (20) or a prooxidant generating ROS (23)(24)(25). We previously observed that flavonoids such as silibinin and kaempferol induce cell death through ROS generation (14,15).…”

Section: Discussionmentioning

confidence: 99%

Lycii cortex radicis extract inhibits glioma tumor growth in vitro and in vivo through downregulation of the Akt/ERK pathway

Jeong

Kim²,

Kim³

et al. 2012

Oncol Rep

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Abstract. Lycii cortex radicis (LCR) is a traditional Korean medicinal herb. The present study was undertaken to examine the effect of an LCR extract on glioma cell growth and to determine its molecular mechanism in U87MG human glioma cells. The LCR extract resulted in apoptotic cell death in a dose-and time-dependent manner. The LCR extract-induced cell death was associated with generation of reactive oxygen species (ROS). Western blot analysis showed that the LCR extract caused downregulation of Akt and ERK. The LCR-induced cell death was prevented by transfection with the constitutively active forms of Akt and MEK. Oral administration of LCR extracts in subcutaneous U87MG xenograft models reduced glioma tumor volume. Taken together, these findings suggest that the LCR extract results in human glioma cell death through mechanisms involving ROS generation, downregulation of Akt and ERK, and caspase activation in vitro and reduces glioma tumor growth in vivo. These data suggest that the LCR extract may serve as a potential therapeutic agent for malignant human glioblastomas.

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Section: Discussionmentioning

confidence: 99%

Lycii cortex radicis extract inhibits glioma tumor growth in vitro and in vivo through downregulation of the Akt/ERK pathway

Jeong

Kim²,

Kim³

et al. 2012

Oncol Rep

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“…Among these six active compounds, fisetin, kaempferol, morin, myricetin and quercetin belong to flavonols and luteolin belong to flavones. Flavonoids are well-known antitumor, antioxidant, and anti-inflammation agents and previous structure-activity analysis has indicated that number and location of OH substitutions are important for the biological effects of flavonoids 21 . Obviously, the active flavonoids in this study contain four or more hydroxyl groups and hydroxylation at the 3′-and or the 4′-position of the B ring seemed of special importance.…”

Section: Inhibition Of Cd-mmp-1 By Flavonoidsmentioning

confidence: 99%

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

Lü

Zhu

Zou

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…23 DCHF-DA is a stable fluorescent ROS-sensitive compound, which readily diffuses into cells. DCHF-DA is hydrolyzed by esterase to form DCHF within cells, which is oxidized by hydrogen peroxide or low-molecular-weight peroxides to produce the fluorescent compound 2 0 ,7 0 -dichlorofluorescein (DCF).…”

Section: Analysis Of Ros Productionmentioning

confidence: 99%

Gossypol reduction of tumor growth through ROS‐dependent mitochondria pathway in human colorectal carcinoma cells

Shen

Yang

et al. 2007

Intl Journal of Cancer

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Among 13 different cell lines, gossypol (GOS) showed the most potent cytotoxic effect against human colorectal carcinoma cells including HT29, COLO205, COLO320HSR and COLO320DM cells according to an MTT assay. The cytotoxic effect of GOS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in both COLO205 and HT29 cells. Activation of caspase 3, 6, 8 and 9, but not caspase 1, accompanied by the appearance of cleaved fragments of PARP (85 kDa), and caspase 3 (p17/ p15), was identified in GOS-treated cells. Decreases in Bcl-xL and phosphorylated Bad proteins were found in GOS-treated cells. GOS induction of ROS production was detected by in vitro plasmid digestion, and an increase in the intracellular peroxide level was observed in GOS-treated COLO205 cells by the DCHF-DA assay. Antioxidants including N-acetyl-L-cysteine (NAC), catalase (CAT), tempol (TEM) and melatonin (MEL), but not allopurinol (ALL), pyrrolidine dithiocarbamate (PDTC) or diphenylene iodonium (DPI), significantly inhibited GOS-induced Reactive oxygen species (ROS) production through blocking the occurrence of apoptosis. GOS induced mitochondrial dysfunction characterized by a loss of the mitochondria membrane potential via DiOC6 staining, and the release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) from mitochondria to the cytoplasm was observed. Removing mitochondria by ethidium bromide (EtBr) treatment significantly reduced the apoptotic effect of GOS in COLO205 cells. Furthermore, an intraperitoneal injection of GOS or gossypol acetic acid (GAA) significantly reduced the growth of colorectal carcinoma induced by a subcutaneous injection of COLO205 cells in nude mice. Results of the present study provide the first evidences demonstrating the in vitro and in vivo antitumor effects of GOS via an ROS-dependent mitochondrial apoptosis in colorectal carcinoma. ' 2007 Wiley-Liss, Inc.

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Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production

Cited by 20 publications

References 0 publications

Lycii cortex radicis extract inhibits glioma tumor growth in vitro and in vivo through downregulation of the Akt/ERK pathway

Lycii cortex radicis extract inhibits glioma tumor growth in vitro and in vivo through downregulation of the Akt/ERK pathway

The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors

Gossypol reduction of tumor growth through ROS‐dependent mitochondria pathway in human colorectal carcinoma cells

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