Gossypol Inhibits Electron Transport and Stimulates ROS Generation in Yarrowia lipolytica Mitochondria

Apogossypolone (ApoG2), a novel derivative of gossypol, exhibits superior antitumor activity in Bcl-2 transgenic mice, and induces autophagy in several cancer cells. However, the detailed mechanisms are not well known. In the present study, we showed that ApoG2 induced autophagy through Beclin-1- and reactive oxygen species (ROS)-dependent manners in human hepatocellular carcinoma (HCC) cells. Incubating the HCC cell with ApoG2 abrogated the interaction of Beclin-1 and Bcl-2/xL, stimulated ROS generation, increased phosphorylation of ERK and JNK, and HMGB1 translocation from the nucleus to cytoplasm while suppressing mTOR. Moreover, inhibition of the ROS-mediated autophagy by antioxidant N-acetyl-cysteine (NAC) potentiates ApoG2-induced apoptosis and cell killing. Our results show that ApoG2 induced protective autophagy in HCC cells, partly due to ROS generation, suggesting that antioxidant may serve as a potential chemosensitizer to enhance cancer cell death through blocking ApoG2-stimulated autophagy. Our novel insights may facilitate the rational design of clinical trials for Bcl-2-targeted cancer therapy.

show abstract

“…Similar results were found in gossypol-treated cells, 36 the mechanism may be through inhibiting electron transport in the mitochondria. 37 …”

Section: Discussionmentioning

confidence: 99%

The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma cells

Cheng

Dai

et al. 2013

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…In the same fashion, gossypol, a triterpenoid aldehyde isolated from cotton plants, was shown to inhibit mitochondrial electron transfer and stimulate generation of ROS (Arinbasarova et al, 2012). Thus, ROS produced by redox-active phenols may have a crucial role in the inhibition of V-ATPase and induction of lipid peroxidation, as well as depletion of anti-oxidant enzyme activities, such as superoxide dismutase, catalase and glutathione peroxidase.…”

Section: Discussionmentioning

confidence: 97%

Potent nematicidal activity of phenolic derivatives on Meloidogyne incognita

2017

View full text Add to dashboard Cite

The present study describes the nematicidal activity of ten selected phenolic derivatives using the root knot nematode, Meloidogyne incognita, model. Nematicidal activity was then correlated with the anti-oxidant power. The highest nematicidal activity was recorded for p-nitrophenol followed by m-nitrophenol, o-nitrophenol and p-bromophenol, with an EC50 after 1 day of immersion of about 0.70 ± 0.64, 8.14 ± 5.49, 15.79 ± 10.81 and 25.92 ± 11.37 μg/ml, respectively. The structure-activity relationship indicates that the nitro-group at position 4 on the phenolic ring (p-nitrophenol) is very important for nematicidal activity, followed by that at position 2 (o-nitrophenol) and position 3 (m-nitrophenol). p-Nitrophenol showed the highest nematicidal activity with the corresponding lowest anti-oxidant activity of about 97 ± 20 μg/ml. In conclusion, these findings suggest that phenolic derivatives could be considered as potent nematicidal agents and be integrated in the pest-management system.

show abstract

“…In addition to its harmful effects, gossypol and its derivatives have potential therapeutic use. These compounds showed in vitro action against some viruses such as human immunodeficiency virus [ 23 , 24 ] and H5N1 influenza virus [ 24 , 25 ] and several bacteria and yeasts [ 26 – 29 ]. Gossypol is a promising treatment for leukemia [ 30 ], lymphoma [ 31 ], colon carcinoma [ 32 ], breast cancer [ 33 , 34 ], myoma [ 35 ], prostate cancer [ 36 ], and other malignancies [ 37 – 43 ].…”

Section: Gossypol In Cotton Productsmentioning

confidence: 99%

Gossypol Toxicity from Cottonseed Products

Gadelha

Fonseca

Oloris

et al. 2014

The Scientific World Journal

213

174

View full text Add to dashboard Cite

Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.). Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal's resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

show abstract

Gossypol Inhibits Electron Transport and Stimulates ROS Generation in Yarrowia lipolytica Mitochondria

Cited by 14 publications

References 19 publications

The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma cells

The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma cells

Potent nematicidal activity of phenolic derivatives on Meloidogyne incognita

Gossypol Toxicity from Cottonseed Products

Contact Info

Product

Resources

About