Anti-angiogenic therapy is widely being used to halt tumour angiogenesis. In this study, the anti-angiogenic activity of palm tocotrienol-rich fraction (TRF) and its individual components (?- and ?-tocotrienol) were first investigated in vitro in human umbilical vein endothelial cells (HUVEC) and 4T1 mouse mammary cancer cells. Results showed reduced levels of Interkeukin (IL)-8 and IL-6, two pro-angiogenic cytokines in HUVEC treated with palm tocotrienols compared with ?-tocopherol (?-T) and control cells (P < 0.05). The production of IL-8 and IL-6 was lowest in ?-tocotrienol (?-T3)-treated cells followed by ?-tocotrienol (?-T3) and TRF. There was significant (P < 0.05) reduction in IL-8 and vascular endothelial growth factor (VEGF) production in 4T1 cells treated with TRF or ?-T3. There was decreased expression of VEGF and its receptors; VEGF-R1 (fms-like tyrosine kinase, Flt-1) and VEGF-R2 (Kinase-insert-domain-containing receptor, KDR/Flk-2) in tumour tissues excised from mice supplemented with TRF were observed. There was also decreased expression of VEGF-R2 in lung tissues of mice supplemented with TRF. These observations correlate with the smaller tumour size recorded in the tocotrienol-treated mice. This study confirms previous observations that palm tocotrienols exhibit anti-angiogenic properties that may inhibit tumour progression.

Several mechanisms have been postulated for the anticancer effects of tocotrienols. In this study, for the first time, the anticancer effect of tocotrienols is linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have antitumor effects in many cancer models. Tocotrienol isomers (α-T3, γ-T3, and δ-T3) and tocotrienol-rich fraction (TRF) inhibited the growth of the 4T1 murine mammary cancer cells (P < 0.05), with IC50 values 8.99, 4.79, 3.73, and 8.63 μg/mL, respectively. Tumor incidence and tumor load in TRF-supplemented BALB/c mice was decreased by 57.1% and 93.6% (P < 0.05), respectively. The induction of the IL-24 mRNA in the 4T1 cells by vitamin E decreased in the following order: δ-T3 > γ-T3 > TRF > α-T3 > α-T, which was similar to their antiproliferative effects. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased 2-fold when compared with control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. Treatment of 4T1 cells with TRF and δ-T3 significantly decreased IL-8 and vascular endothelial growth factor mRNA levels. Hence, we report that tocotrienols have potent antiangiogenic and antitumor effects that is associated with increased levels of IL-24 mRNA.

Introduction: Excess bodyweight or adiposity is an epidemic health problem that increases the risk of various types of cancer. Adipose tissue produces hormones known as adipocytokines, which participate in carcinogenesis in many solid tumours. Leptin was shown to have mitogenic effects in cancer cell lines thus promoting the malignant behavior of cancer. Adiponectin has a significant anti-inflammatory effect and showed an inverse relation with solid tumours risk. It was hypothesized that adiponectin provides protection against carcinogenesis. However, the knowledge on the relation of adiposity and adipocytokines with haematological malignancies is limited and the findings were not consistent. Materials and Methods: We studied this feature in newly diagnosed haematological malignancy cases in Malaysia. Diagnosis was made according to World Health Organization (WHO) guidelines or the French-American-Britain (FAB) classification. The body mass index (BMI), waist hip ratio, adipocytokines levels (leptin and adiponectin) were measured in subjects (n=29) and healthy control (n=18). Results: There was no significant difference in the mean BMI of control and subjects. However, the mean waist hip ratio in subjects were significantly higher (0.91) compared to control (0.82) with p=0.04. The mean level of leptin was markedly raised in subjects compared to control (1.80 vs 17.41) with p=0.00. The mean adiponectin level was significantly suppressed in subjects (6.54 vs 0.15) with p=0.00. Discussion: This study supports the evidence that adiposity and adipocytokines are related to haematological malignancy similar to that of solid tumours. We also concluded that waist hip ratio is a better index of adiposity compared to BMI.