Cellular and molecular mechanisms involved in the antiproliferative action of [10]-gingerol on breast tumor cells

• Grant number: 12/18908-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2013
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Angelina Maria Fuzer
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 15/08146-0 - Effects of [10]-gingerol on three-dimensional tumor microenvironment, BE.EP.DD

Abstract

Cancer is the second leading cause of death worldwide, preceded by cardiovascular diseases. Despite many therapeutic advances in the field, mortality is still high. For the year 2050, the estimation is the emergence of 24 million new cases of cancer in the world, with a total of 16 million deaths. Cancer, therefore, will be one of the main challenges in the area of public health in the coming years, both in developing countries as in developed countries. The development of antitumor drugs is a field full of challenges. The ideal chemotherapeutic agent should act to selectively kill or inhibit the growth of cancer cells, leaving normal cells intact. However, most drugs currently used in chemotherapy causes DNA damage both in tumor cells as well as in normal cells, causing the undesirable side effects associated with chemotherapy. Another feature of many chemotherapy drugs is that they act only at specific stages of the tumor cell cycle, creating drug resistance conditions and enabling cells to respond treatment. These peculiarities pose a major challenge to the antitumor drugs area and, therefore, the creening of candidate compounds for new drugs becomes an extremely complex and challenging, however indispensable field of research. Several population-based studies indicate that people living in Asian countries have a much lower risk of being affected by different cancer types, compared with their Western counterparts. It is widely known that the constituents of the Oriental diet, such as ginger, garlic, soy, curcumin, onion, tomatoes, cruciferous vegetables, pepper and green tea contribute to this lower incidence. Therefore, there is a growing interest in the study of components naturally occurring in these foods, in an attempt to demonstrate their antitumor abilities and their use as the basis for the design of new anticancer drugs. Ginger (Zingiber officinale Roscoe) is widely used worldwide as a food and spice. Together with [6]-gingerol, the [8]- and [10]-gingerol are the major constituents of ginger. Regarding the [6]-gingerol a variety of pharmacological properties has been described, including analgesic, antipyretic and antitumor, among others. However, the effects on proliferation, invasion, migration and apoptotic effects on tumor cells by [8]- and [10]-gingerol are still scarce. In a previous study with the compounds [6]-, [8]- and [10]-gingerol, it was found that these substances possess antiproliferative activities more intense in the breast tumor cell line, MDA-MB-231 when compared to non-tumor cells, human fibroblasts (HF). These activities were greater the greater the alkyl chain derivatives of ginger. Namely, [6]-, [8]- and [10]-gingerol inhibited the proliferation of tumor cells with ICs50 666.2±134.6uM, 135.6±22.6uM and 12.1±0.3uM, respectively. Therefore, the objective of this study is to evaluate the cellular and molecular mechanisms involved in the antiproliferative effects of [10]-gingerol performing cell adhesion assays, using both static and flow conditions, migration, transmigration, invasion and apoptosis assays as well verifying the expression of genes involved in apoptotic, cell migration and invasion pathways. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARTIN, ANA CAROLINA B. M.; FUZER, ANGELINA M.; BECCENERI, AMANDA B.; DA SILVA, JAMES ALMADA; TOMASIN, REBEKA; DENOYER, DELPHINE; KIM, SOO-HYUN; MCINTYRE, KATHERINE A.; PEARSON, HELEN B.; YEO, BELINDA; et al. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo. ONCOTARGET, v. 8, n. 42, p. 72260-72271, SEP 22 2017. (12/03771-5, 13/00798-2, 15/24940-8, 12/18908-6)

MARTIN, ANA CAROLINA B. M.; FUZER, ANGELINA M.; BECCENERI, AMANDA B.; DA SILVA, JAMES ALMADA; TOMASIN, REBEKA; DENOYER, DELPHINE; KIM, SOO-HYUN; MCINTYRE, KATHERINE A.; PEARSON, HELEN B.; YEO, BELINDA; et al. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer invivo. ONCOTARGET, v. 8, n. 42, p. 12-pg., 2017-09-22. (13/00798-2, 12/18908-6, 15/24940-8, 12/03771-5)

FUZER, ANGELINA M.; LEE, SUN-YOUNG; MOTT, JONI D.; COMINETTI, MARCIA R.. [10]-Gingerol Reverts Malignant Phenotype of Breast Cancer Cells in 3D Culture. Journal of Cellular Biochemistry, v. 118, n. 9, p. 2693-2699, SEP 2017. (13/00798-2, 15/08146-0, 12/18908-6)