Section 52
Chapter 51,190

A novel DNA intercalator, 8-methoxy pyrimido[4',5':4,5]thieno (2,3-b) quinoline-4 (3H) -one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Sharma, S.; Panjamurthy, K.; Choudhary, B.; Srivastava, M.; Shahabuddin, M.; Giri, R.; Advirao, G.M.; Raghavan, S.C.

Molecular Carcinogenesis 52(6): 413-425


ISSN/ISBN: 1098-2744
PMID: 22213363
DOI: 10.1002/mc.21867
Accession: 051189519

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Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent.

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