Document Type : Original Article


Personalized Medicine Research Center of AmitisGen, Tehran, Iran



One of the most well-known side effects of anticancer drugs is the disruption of spermatogenesis. One of the most important causes of infertility in men is impaired spermatogenesis. Busulfan is a cytotoxic alkylating agent and belongs to the alkyl sulfonate group. This agent causes DNA damage by cross-linking with DNA. It kills spermatogonial stem cells. The use of healthy antioxidants can reduce the side effects of alkylating agents. In this study, we measured the protective effect of curcumin on testicular tissue of mice treated with busulfan by measuring BAX expression as an apoptotic inducer and Bcl2 as an apoptotic inhibitor. The expression levels of the two apoptotic regulatory genes Bax and Bcl-2 were evaluated by realtime PCR in four groups of mice (control, treatment with busulfan, treatment with curcumin, and treatment with busulfan + curcumin). It was observed in the busulfan group that bcl2 expression decreased, and Bax increased significantly, and the busulfan + curcumin group showed the opposite effect. Curcumin can be beneficial as a dietary supplement in cancer patients treated with drugs such as busulfan.


1. McGuire S. World cancer report 2014. Geneva, Switzerland:
World Health Organization, international agency for research
on cancer, WHO Press, 2015. Oxford University Press, 2016
2. Rahimi Pordanjani S, Baeradeh N, Lotfi MH,
Pourmohammadi B. Epidemiology of colorectal cancer:
incidence, mortality, survival rates and risk factors. Razi J Med
Sci. 2016;23(144):41-50.
3. Tanis PJ, Doeksen A, van Lanschot JJ. Intentionally curative
treatment of locally recurrent rectal cancer: a systematic
review. Can J Surg. 2013;56(2):135-144. doi:
10.1503/cjs.025911 pmid: 23517634
4. DeVita VT, Jr., Chu E. A history of cancer chemotherapy.
Cancer Res. 2008;68(21):8643-8653. doi: 10.1158/0008-
5472.CAN-07-6611 pmid: 18974103
5. Muller J, Skakkebaek NE, Hertz H. Initiation of
spermatogenesis during chemotherapy for leukemia. Acta
Paediatr Scand. 1985;74(6):956-960. doi: 10.1111/j.1651-
2227.1985.tb10064.x pmid: 3867220
6. de Kretser DM, Loveland KL, Meinhardt A, Simorangkir D,
Wreford N. Spermatogenesis. Hum Reprod. 1998;13 Suppl
1:1-8. doi: 10.1093/humrep/13.suppl_1.1 pmid: 9663765
7. Hassan M, Ljungman P, Bolme P, Ringden O, Syruckova Z,
Bekassy A, et al. Busulfan bioavailability. Blood.
1994;84(7):2144-2150. pmid: 7919328
8. Jiang FX. Behaviour of spermatogonia following recovery from
busulfan treatment in the rat. Anat Embryol (Berl).
1998;198(1):53-61. doi: 10.1007/s004290050164 pmid:
9. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.
Bioavailability of curcumin: problems and promises. Mol
Pharm. 2007;4(6):807-818. doi: 10.1021/mp700113r pmid:
10. Choi YJ, Ok DW, Kwon DN, Chung JI, Kim HC, Yeo SM, et
al. Murine male germ cell apoptosis induced by busulfan
treatment correlates with loss of c-kit-expression in a
Fas/FasL- and p53-independent manner. FEBS Lett.
2004;575(1-3):41-51. doi: 10.1016/j.febslet.2004.08.034
pmid: 15388331
11. Shaha C, Tripathi R, Mishra DP. Male germ cell apoptosis:
regulation and biology. Philos Trans R Soc Lond B Biol Sci.
2010;365(1546):1501-1515. doi: 10.1098/rstb.2009.0124
pmid: 20403866
12. Bahmanpour S, Namavar Jahromi B, Koohpeyma F, Keshavarz
M, Bakhtari A. Research Paper: Effects of Different Doses and
Time-Dependency of Busulfan on Testes Parameters and
Spermatogenesis in a Rat Model: A Quantitative Stereological
Study. J Adv Med Sci Applied Tech. 2019;3(3):155-162. doi:
13. Moloody M, Shahrooz R, Razi M, Zarei L, Mohammadi V. The
Effect of CoQ10 on Testicular Tissue in Rats Treating with
Busulfan: Sperm Quality and Histological Changes. Iran J Vet
Surg. 2018;13(1):29-38.