NDLI: Rosamines Targeting the Cancer Oxidative Phosphorylation Pathway

Content Provider	PubMed Central
Author	Lim, Siang Hui Wu, Liangxing Voon, Kiew Lik Chung, Lip Yong Burgess, Kevin Lee, Hong Boon
Editor	Pandey, Siyaram
Copyright Year	2014
Abstract	Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = −7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.
Related Links	http://dx.doi.org/10.1371/journal.pone.0082934
Starting Page	82934
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	3
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-03-12
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The emerging role of targeting cancer metabolism for cancer therapy

Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia

γ-tocotrienol regulates gastric cancer by targeting notch signaling pathway

Counteracting oxidative phosphorylation-mediated resistance of melanomas to MAPK pathway inhibition

Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest

Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer

Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer

Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation

Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and Oxidative Phosphorylation in melanoma

Rosamines Targeting the Cancer Oxidative Phosphorylation Pathway

Similar Documents

The emerging role of targeting cancer metabolism for cancer therapy

Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia

γ-tocotrienol regulates gastric cancer by targeting notch signaling pathway

Counteracting oxidative phosphorylation-mediated resistance of melanomas to MAPK pathway inhibition

Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest

Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer

Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer

Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation

Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and Oxidative Phosphorylation in melanoma

Rosamines Targeting the Cancer Oxidative Phosphorylation Pathway