Zeitschrift für Karzinogenese und Mutagenese

Abstrakt

Sulforaphane Inhibits Metastatic Events in Breast Cancer Cells through Genetic and Epigenetic Regulation

Madhumita Roy, Ruma Sarkar, Sutapa Mukherjee, Apurba Mukherjee and Jaydip Biswas

Metastasis is a deadly event in carcinogenesis, which is regulated both genetically as well as epigenetically. Regulation of key molecules involved in this phenomenon could be a promising strategy in cancer control.

The epigenetic enzyme HDAC6 along with telomerase and HSP90, two genetic markers of carcinogenesis are implicated in the metastatic pathway. Therefore, modulation of these markers may aid in prevention of spread of cancer to distant parts. Plant derived molecules are apparently nontoxic and stud with anticancer activities. Present study aims to investigate the effect of sulforaphane (Sfn), an organosulfur compound on these markers, which might be helpful in inhibition of metastasis.

It was observed that sulforaphane significantly inhibited HDAC6 expression, both at protein and genetic level in metastatic breast cancer cell MDA-MB-231. Inhibition of HDAC6 was associated with increased acetylation of HSP90 and diminished expression of transcription factor c-myc. These results were further confirmed by using tubacin, a specific HDAC6 inhibitor. Activity and expression of human telomerase reverse transcriptase, a main determinant of catalytic activity of the enzyme was found to be inhibited by Sfn. Repression of c-myc led to transcriptional down-regulation of hTERT mRNA and de-repression of p21. Modulation of these proteins led to down-regulation of VEGF and MMPs (2 and 9), two key players of the metastatic event. Regulation of these proteins by Sfn decelerates migration and invasion of the metastatic breast cancer cells, thereby showing anti-metastatic potential.

Sulforaphane, by virtue of its modulatory role on HDAC6 and other associated proteins may lead to inhibition of metastasis in breast cancer cells.