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

Abstract

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.

Sapodilla Plum (Achras sapota) Induces Apoptosis in Cancer Cell Lines and Inhibits Tumor Progression in Mice

“…Breast adenocarcinoma derived EAC cells are predominantly used for inducing tumors in mice as well as for assessing the anticancer activity of compounds in vivo 103334. Our results showed that MESF treatment in mice bearing tumor resulted in significant reduction in tumor volume.…”

“…Cells were counted under a microscope after trypan blue staining and plotted as described earlier373839. Alternatively, we also monitored the ratio of live to dead cells following addition of MESF (0, 0.75, 1.0, 2.0 and 5 mg/ml) in total cell population by Live-Dead cell assay using flow cytometry as described33. Experiments were repeated a minimum of three times and data is presented as bar diagram with error bars.…”

“…A fixed number of viable EAC cells collected from donor mice were injected into the peritoneal cavity of each recipient mouse and were allowed to multiply. The cells were withdrawn after 8–10 days of inoculation, diluted in saline (1 × 10 6  cells/animal) and injected to left thigh of experimental animals for developing the solid tumor3334.…”

“…The increase in life span of MESF treated mice was calculated and compared with untreated tumor bearing animals. The life span of experimental animals was monitored and calculated by using the formula ((T − C)/C) × 100, where ‘T' indicates the number of days the treated animals survived and ‘C' indicates that number of days that tumor animals survived3334.…”

“…Control mice received equal volume of water as the MESF was dissolved in it. Tumor size was measured using vernier calipers on alternative days for tumor animals and tumor volume was calculated using the formula V = 0.5 × a × b 2 , where ‘a' and ‘b' indicates the major and minor diameter, respectively3334. At the end of 16 th day of experimental period, animals from each group were sacrificed and kidney, liver, thigh and spleen were collected from normal, tumor and Sapota fruit extracts treated animals and were evaluated for morphological changes.…”