We previously observed that chronic consumption of a high-fat diet (HFD) increased the melanoma progression and lymph node metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils especially clove and oregano oils. In the present study, we examined whether BCP inhibits HFD-induced melanoma growth and metastasis in the B16F10 allograft model. Four-week old, male C57BL/6 mice were fed on a HFD (60 kcal% fat) or control diet (CD, 10 kcal% fat) with or without BCP (0.15, 0.3% in diet) for a period of 21 weeks. Following 16 weeks of either CD or HFD in the absence or presence of BCP, B16F10 melanoma cells were subcutaneously injected into mice and all mice were continuously fed identical diets. Three weeks post-injection, tumors were resected and mice were sacrificed three weeks post-resection. The body weights and the growth of solid tumors were markedly increased in the HFD group as compared to the CD group, and these increases were suppressed by BCP treatment. The expression of proteins related to cell proliferation (Ki67, CDK4, cyclin A, and cyclin D1), angiogenesis (VEGF-A, VEGFR-2, and CD31) and lymphangiogenesis (VEGF-C, VEGF-D, VEGFR-3, and LYVE-1) was markedly increased in tumor tissues of the HFD group as compared to the CD group, and these increases were blocked by BCP treatment. HFD feeding increased the infiltration of CD45+ leukocytes and F4/80+ macrophages into tumor tissues. The administration of BCP significantly suppressed HFD-induced the infiltration of the immune cells into tumor tissues. HFD feeding reduced TUNEL-positive apoptotic cells in the tumor tissues, which was prevented by BCP treatment. Two weeks after tumor resection, the mice evidenced lung and lymph node metastasis. Lung and lymph node metastasis were increased in the mice fed on HFD, and these increases were markedly suppressed by BCP treatment. The present results demonstrate that BCP suppressed HFD-stimulated melanoma progression and metastasis, which may have been mediated via the suppression of cell cycle progression, angiogenesis and lymph angiogenesis, and induction of apoptosis in tumor tissues. These results suggest that BCP has potential as an anti-cancer agent for the prevention of obesity-stimulated melanoma progression.
Citation Format: Jae In Jung, Eun Ji Kim, Yoo Jin Jung, Hyang Sook Chun, Jung Han Yoon Park. β-caryophyllene inhibits solid tumor growth and metastasis of B16F10 melanoma cells in C57BL/6 mice fed on a high-fat diet. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4869. doi:10.1158/1538-7445.AM2013-4869