Induction of apoptosis by -gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis
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To unravel the molecular mechanisms underlying the chemopreventive potential of -gingerol, a pungent ingredient of ginger rhizome (Zingiber officinale Roscoe, Zingiberaceae), against benzo[a]pyrene (B[a]P)-induced mouse skin tumorigenesis.
Topical treatment of -gingerol (2.5 μM/animal) was given to the animals 30 min prior and post to B[a]P (5 μg/animal) for 32 weeks. At the end of the study period, the skin tumors/tissues were dissected out and examined histopathologically. Flow cytometry was employed for cell cycle analysis. Further immunohistochemical localization of p53 and regulation of related apoptogenic proteins were determined by Western blotting.
Chemopreventive properties of -gingerol were reflected by delay in onset of tumorigenesis, reduced cumulative number of tumors, and reduction in tumor volume. Cell cycle analysis revealed that the appearance of sub-G1 peak was significantly elevated in -gingerol treated animals with post treatment showing higher efficacy in preventing tumorigenesis induced by B[a]P. Moreover, elevated apoptotic propensity was observed in tumor tissues than the corresponding non-tumor tissues. Western blot analysis also showed the same pattern of chemoprevention with -gingerol treatment increasing the B[a]P suppressed p53 levels, also evident by immunohistochemistry, and Bax while decreasing the expression of Bcl-2 and Survivin. Further, -gingerol treatment resulted in release of Cytochrome c, Caspases activation, increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction.
On the basis of the results we conclude that -gingerol possesses apoptotic potential in mouse skin tumors as mechanism of chemoprevention hence deserves further investigation.
KeywordsMouse skin tumorigenesis -Gingerol Benzo(a)pyrene Chemoprevention Apoptosis
Authors are thankful to Director Indian Institute of Toxicology Research, Lucknow (Council of Scientific & Industrial Research, India) for his keen interest in the study. We are thankful to Dr. Neeraj Mathur, Scientist for statistically analyzing the data. Authors are also thankful to Department of Biotechnology (India) and Council of Scientific & Industrial Research, New Delhi (under NWP-17) for jointly funding this work.
- 14.Bogovaski P (1979) Tumours of skin. In: Turusov VS (ed) Pathology of tumours in laboratory animals, vol II, Tumours of the mouse, IARC scientific publication no. 23. IARC, LyonGoogle Scholar
- 23.Safe S, Wargovich MJ, Lamartiniere CA, Mukhtar H (1999) Symposium on mechanisms of action of naturally occurring anticarcinogens. Toxicol Sci 52:1–8Google Scholar