Ahmed, Sarfraz
(2015)
The mechanism of anticarcinogenic effects of tualang honey (TH) on induced breast cancer in rats.
Masters thesis, Universiti Sains Malaysia.
Abstract
The multifloral Tualang honey (TH) and the monofloral Manuka honey (MH) have been
reported to have antimicrobial, anti-inflammatory, antioxidant and anticancer effects. Unlike the
Manuka honey, TH is not extensively studied. We conducted a study to evaluate the mechanisms
of the preventive and therapeutic effects of TH and MH on experimental breast cancer induced
rats using carcinogen 1-methyl-1-nitrosourea (MNU). We also conducted a similar cancer
therapeutic study using Honey sugars analogue (HSA), a fluid which contains the proportion of
sugars in honey. A total of 130 female Sprague-Dawley rats were used. Sixty female rats were
randomly divided into 6 groups with 10 animals per group in each study. Group ‘0’ did not
receive MNU and did not receive honey (negative Control); Group 1 received MNU but not
honey/honey sugars analogue (positive Control). Groups 2, 3 and 4 were fed orally with 0.2, 1.0,
2.0, 1.0 g/kg body weight of TH, and Group 5 received 1.0 g/kg body weight of MH. Group 6
received 1.0 g/kg body weight of HSA in therapeutic study. For the “cancer-preventive” study,
honey was given one week prior to MNU-induction and for the “cancer-therapeutic” study;
honey was given when the first palpable tumor reached 10-12 mm in size. The development of
mammary tumors and body weights were charted throughout the study. The rats in all treated
groups continued to receive the treatment until the 120th day when they were sacrificed. At
autopsy, blood was drawn for haematological and serological analysis. The tumors were
harvested for gross and histopathological examinations, and determination of pro and antiapoptotic
proteins expression by immunohistochemistry using a panel of antibodies. Results
showed that TH and MH treated rats of “cancer-preventive” groups had a lower tumor incidence
(the number of animals developing tumors), and a longer latency period (the interval when the
first tumor developed after MNU induction) compared to the non-treated control group. The
number of tumors developed in the treated groups was lesser than the non-treated control group
(p˂0.05). Regardless of honey treatment given, either before or after the breast cancer
development, the tumors had slower size increment (˂1.48 cm3 and ˂2 cm3 for cancer
preventive and therapeutic effects respectively) compared to the non-treated control group (=2.85
cm3 and =3.84 cm3 respectively). The median weight (g) and size (cm3) of the tumors in treated
groups were also significantly lower (p˂0.05). A significant actual body weight gain was
Histopathological examination showed various tumor patterns; ranging from benign, DCIS
(ductal carcinoma in situ), micropapillary and NOS (not-otherwise specified) type. The treated
groups showed more patterns of benign tumors compared to the non-treated control group. The
majority of the tumors in the treated groups were of better grade (grade І and ІІ) compared to the
non-treated control group (grade ІІІ). The haematological parameters showed that different
dosages of TH, MH and HSA had an increasing effect on Hb (haemoglobin), RBC (red blood
cells), PCV (packed cell volume), MCV (mean corpuscular volume), lymphocytes and
eosinophils counts compared to the non-treated positive control. Treatments with TH, MH and
HSA presented a decreasing effect on TWBC (total white blood cells), RDW (red cell
distribution width), polymorphs, monocytes and platelets counts compared to the non-treated
positive control. Various preparations of TH, MH and HSA showed no hyperglycemic effect on
fasting blood glucose level. Serum biochemistry showed that the rats treated with TH, MH and
HSA had an increased level of pro-apoptotic proteins; Apaf-1 (apoptotic protease activating
factor 1) and IFN-
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