School Of Basic And Applied Sciences

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    The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer
    (Impact Journals LLC, 2017) Malhotra, Akshay; Jain, Manju; Prakash, Hridayesh; Vasquez, Karen M.; Jain, Aklank; Malhotra, A.; Jain, M.; Prakash, H.; Vasquez, K.M.; Jain, A.
    Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy. ? 2017 Malhotra et al.
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    Intracellular delivery of redox cycler-doxorubicin to the mitochondria of cancer cell by folate receptor targeted mitocancerotropic liposomes
    (2012) Malhi, Sarandeep Singh; Budhiraja, Abhishek; Arora, Sumit; Chaudhari, Kiran R.; Nepali, Kunal; Kumar, Raj; Sohi, Harmik; Murthy, Rayasa S.R.
    Cancer cells reflect higher level of ROS in comparison to the normal cell, so they become more vulnerable to further oxidative stress induced by exogenous ROS-generating agents. Through this a novel therapeutic strategy has evolved, which involves the delivery of redox cycler-doxorubicin (DOX) to the mitochondria of cancer cell where it acts as a source of exogenous ROS production. The purpose of this study is to develop a liposomal preparation which exhibits a propensity to selectively target cancer cell along with the potential of delivering drug to mitochondria of cell. We have rendered liposomes mitocancerotropic (FA-MTLs) by their surface modification with dual ligands, folic acid (FA) for cancer cell targeting and triphenylphosphonium (TPP) cations for mitochondria targeting. The cytotoxicity, ROS production and cell uptake of doxorubicin loaded liposomes were evaluated in FR (+) KB cells and found to be increased considerably with FA-MTLs in comparison to folic acid appended, mitochondria targeted and non-targeted liposomes. As confirmed by confocal microscopy, the STPP appended liposomes delivered DOX to mitochondria of cancer cell and also showed higher ROS production and cytotoxicity in comparison to folic acid appended and non-targeted liposomes. Most importantly, mitocancerotropic liposomes showed superior activity over mitochondria targeted liposomes which confirm the synergistic effect imparted by the presence of dual ligands - folic acid and TPP on the enhancement of cellular and mitochondrial delivery of doxorubicin in KB cells. ? 2012 Elsevier B.V. All rights reserved.