Non-addictive opium alkaloids selectively induce apoptosis in cancer cells compared to normal cells - PubMed (original) (raw)

Non-addictive opium alkaloids selectively induce apoptosis in cancer cells compared to normal cells

Monireh Afzali et al. Daru. 2015.

Abstract

Background: Cytotoxic effects of some of the members of papaveraceae family have been reported in Iranian folk medicine. Recent reports has indicated that alkaloids fraction of opium may be responsible for its cytotoxic effect; however, the mechanism of this effect is not fully understood. This study has been designed to investigate the selective cytotoxic, genotoxic and also apoptosis induction effects of noscapine, papaverine and narceine, three non-addictable opium alkaloids, on HT29, T47D and HT1080 cancer cell lines. Mouse NIH3T3 cell line was chosen to present non-cancerous cells and Doxorubicin was selected as the positive control.

Methods: Cells were treated by different concentrations of Noscapine, Papaverine, Narceine and doxorubicin; viability was assessed by MTT assay. The genotoxicity and apoptosis induction were tested with comet assay and Annexin-V affinity when the concentration of each these drugs is less than its IC50. In addition, the DNA damage and caspase activity of the T47D cells were examined and the results were compared.

Results: This study noted the cytotoxicity and genotoxicity of noscapine and papaverine, specifically on cancerous cell lines. Furthermore, papaverine induces apoptosis in all studied cancer cell lines and noscapine showed this effect in T47D and HT29 cells but not in NIH-3 T3 cells as noncancerous cell line. narceine also showed genototoxicity in the studied cell lines at its IC50 concentration.

Conclusions: This experiment suggests that noscapine and papaverine may be of use in cancer treatment due to their specific cytotoxicity and genotoxicity. However, further in vivo studies are needed to confirm its usefulness in cancer treatment.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Cytotoxic effects of opium alkaloids and doxorubicin on cell lines. Cell viability in each treatment group was determined by MTT assay at 570 nm in reference standard at 690 nm. The IC50 values were calculated based on their cytotoxicity dose–response curve using Sigmaplot software and the results are expressed as Mean ± SD. a: HT29, b: T47D, c: HT1080 and d: NIH-3 T3.

Figure 2

Figure 2

The DNA damage detected in treated cells compared to control group. The concentrations less than IC50 were used for treatment. The tail length of comet assay has been shown (Mean ± SD) and p-value has been reported. a: HT29, b: T47D, c: HT1080 and d: NIH-3 T3.

Figure 3

Figure 3

The membrane asymmetry comparison between treated cells compared to control group. The concentrations less than IC50 were used for treatment. The percentage of cell population of each quadrant has been shown and the quantitative average of percentage of apoptotic cells of repeated examinations (Mean ± SD) and p-value has been reported. a: HT29, b: T47D, c: HT1080 and d: NIH-3 T3.

Figure 4

Figure 4

Internucleosomal fragmentation of T47D cells. The cells were treated with a: doxorubicin, b: noscapine, c: papaverine and d: narceine then DNA laddering was measured after 48 hours. e: negative control and L: Laddering marker are presented in figure as well.

Figure 5

Figure 5

The activity of caspase-3 after 48 hours incubation of post-treatment T47D cells. Data are reported as mean ± SD. It is shown significant increase in caspase 3 activities after treatment by doxorubicin and noscapine (p < 0.001).

Similar articles

Cited by

References

    1. Goodman LS, Gilman A, Brunton LL, Parker KL, Blumenthal DK, Buxton ILO. Goodman & Gilman’s manual of pharmacology and therapeutics. New Delhi: McGraw-Hill; 2008.
    1. Aruna K, Sivaramakrishnan V. Anticarcinogenic effects of some Indian plant products. Food Chem Toxicol. 1992;30:953–6. doi: 10.1016/0278-6915(92)90180-S. - DOI - PubMed
    1. Healthcare T. PDR for Herbal Medicines. 4, illustrated edn. Montvale: Thomson Healthcare; 2007.
    1. Evans WC. Trease and Evans. WB Saunders Harcourt Publishers Ltd. 2002;292:357–75.
    1. Aneja R, Miyagi T, Karna P, Ezell T, Shukla D, Vij Gupta M, Yates C, Chinni SR, Zhau H, Chung LWK. A novel microtubule-modulating agent induces mitochondrially driven caspase-dependent apoptosis via mitotic checkpoint activation in human prostate cancer cells. Eur J Cancer. 2010;46:1668–78. doi: 10.1016/j.ejca.2010.02.017. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources