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Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Overview of attention for article published in BMC Cancer, January 2017
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Title
Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
Published in
BMC Cancer, January 2017
DOI 10.1186/s12885-016-3005-7
Pubmed ID
Authors

Khayal Al-Khayal, Ahmed Alafeefy, Mansoor-Ali Vaali-Mohammed, Amer Mahmood, Ahmed Zubaidi, Omar Al-Obeed, Zahid Khan, Maha Abdulla, Rehan Ahmad

Abstract

Colorectal cancer (CRC) is the 3(rd) most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Ph. D. Student 5 13%
Student > Master 4 11%
Student > Bachelor 3 8%
Unspecified 2 5%
Other 5 13%
Unknown 12 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 21%
Agricultural and Biological Sciences 4 11%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Immunology and Microbiology 3 8%
Unspecified 2 5%
Other 6 16%
Unknown 12 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 February 2017.
All research outputs
#18,535,896
of 22,957,478 outputs
Outputs from BMC Cancer
#5,464
of 8,344 outputs
Outputs of similar age
#311,416
of 421,535 outputs
Outputs of similar age from BMC Cancer
#74
of 106 outputs
Altmetric has tracked 22,957,478 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,344 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 421,535 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 106 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.