Flaxseed Lignans Enhance the Cytotoxicity of Chemotherapeutic Agents against Breast Cancer Cell Lines MDA-MB-231 and SKBR3.

Key Findings

The purpose of this study was to investigate the ability of several lignan metabolites of SDG, namely SECO, ENL, and ENL-Gluc, to enhance the cytotoxic effect of cancer chemotherapeutics, docetaxel, doxorubicin, and carboplatin, against SKBR3 (HER2 positive) and MDAMB- 231 (triple negative) breast cancer cells in vitro. The in vitro data support the possibility of using flaxseed lignan supplementation as an adjuvant therapy to decrease cytotoxic chemotherapeutic drug dosage requirements while enhancing their effectiveness. Flaxseed lignans, especially ENL, selectively enhanced the cytotoxicity of chemotherapeutic agents with different mechanisms of action in HER2 positive SKBR3 breast cancer cells, and triple-negative MDAMB-231 breast cancer cells. ENL further enhances the efficacy of metformin in combination with cytotoxic chemotherapeutic drugs. The results warrant further in vitro studies to understand the mechanism(s) that contribute to the combination effects observed with cytotoxic chemotherapeutic agents alone or in the case with the newer anticancer agent metformin. Furthermore, human clinical trials should explore the clinical utility of dietary flaxseed lignan supplementation as an adjuvant therapy in patients with heterogenous forms of breast cancer.

ABSTRACT

Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve treatment response, survival rates, and quality of life of breast cancer patients. This study investigated the combination of flaxseed lignans (Secoisolariciresinol and Enterolactone) with classic chemotherapeutic agents (Docetaxel, Doxorubicin, and Carboplatin) with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231. The experimental data suggests that flaxseed lignans significantly enhanced the ability of chemotherapeutic agents to cause cytotoxicity in SKBR3 and MDA-MB-231 breast cancer cells. A three compound combination study found that enterolactone and metformin together in combination with relatively low concentrations of chemotherapeutic drugs were able to significantly decrease cancer cell viability, compared to low concentrations of the individual chemotherapeutic drug alone. Our in vitro evaluation suggests a future direction in improving chemotherapeutic efficacy in breast cancer by adjuvant therapy with the flaxseed lignans.