NDLI: p53 dependent apoptosis and cell cycle delay induced by heteroleptic complexes in human cervical cancer cells.

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Year: 2017 Volume: 89

Year: 2017 Volume: 88

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p53 dependent apoptosis and cell cycle delay induced by heteroleptic complexes in human cervical cancer cells.

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p53 dependent apoptosis and cell cycle delay induced by heteroleptic complexes in human cervical cancer cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sharma, Gunjan Rana, Nishant Kumar Singh, Priya Dubey, Pradeep Pandey, Daya Shankar Koch, Biplob
Description	Author Affiliation: Sharma G ( Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: gunjansharmabhu10@gmail.com.); Rana NK ( Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: rananishant19nov@gmail.com.); Singh P ( Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: priyasinghbhu20@gmail.com.); Dubey P ( Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: gauravcdubey91@gmail.com.); Pandey DS ( Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: dspbhu@bhu.ac.in.); Koch B ( Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: kochbiplob@gmail.com.)
Abstract	We previously reported synthesis of novel arene ruthenium (Ru) complexes and evaluated their antitumor activity in murine lymphoma (DL) cells. In this present study we further investigated the mechanism of action of two ruthenium complexes [complex 1 (Î·6-arene)RuCl(2-pcdpm)] and complex 2 (Î·6-arene)RuCl(4-mtdpm)] in cervical cancer cell line (HeLa). Our studies demonstrate that anticancer property of these two complexes was due to induction of apoptosis through p53 mediated pathway as well as arrest of cells in G2/M phase of cell cycle. It is worth to note that the complexes did not cause any substantial cytotoxic effect on normal cells. Further in comprehensive studies, apoptosis inducing property of both complexes were established in accordance with array of morphological changes ranging from membrane blebbing to formation of apoptotic bodies and followed by DNA fragmentation assay. Furthermore, Flow cytometry by Annexin V/PI staining delineate that complex 1 and 2 have strident impact to induce apoptosis in HeLa cells. The complex 1 and 2 treated cells show increased level of intracellular ROS generation which was preceded by p53 activation. Apoptosis induced by 1 and 2 was preceded by mitochondrial aggregations which were monitored by mitotracker. In addition flow cytometry analysis showed that both complexes also effectively arrest cells at G /M phase of cell cycle. Western blot, RT-PCR as well as Real Time analysis were used to further confirm that the complexes induced apoptosis in p53 dependent pathway. Thus, our promising results can contribute to the rational design of novel potential anticancer agents.
File Format	HTM / HTML
ISSN	07533322
Volume Number	88
e-ISSN	19506007
Journal	Biomedicine & Pharmacotherapy
Language	English
Publisher	Elsevier
Publisher Date	2017-04-01
Publisher Place	France
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Apoptosis Physiology Cell Cycle Checkpoints Tumor Suppressor Protein P53 Uterine Cervical Neoplasms Genetics Cell Cycle Proteins Metabolism Cell Line, Tumor Cell Nucleus Pathology Ultrastructure Dna Fragmentation Female Hela Cells Humans Mitochondria Reactive Oxygen Species Journal Article
Content Type	Text
Resource Type	Article
Subject	Medicine Pharmacology

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