Sorghum polyphenol suppresses the growth as well as metastasis of colon cancer xenografts through co-targeting jak2/STAT3 and PI3K/Akt/mTOR pathways

• Treatment with HSE induced G1 phase arrest and apoptosis in colon cancer cells.
• HSE inhibited Jak2/STAT5b and PI3K/Akt/mTOR pathways.
• HSE inhibited the transcription activation functions of STAT3.
• Colon cancer cell migration and invasion inhibited with HSE treatment.
• Tumor growth as well as pulmonary metastasis inhibited with HSE treatment.

Sorghum contains phytochemicals that can protect against multiple forms of cancers. However, the underlying molecular targets and cellular mechanisms remain unknown. We investigated the role of Hwanggeumchal sorghum extracts (HSE) on colon cancer cells. We found HSE inhibited the proliferation of human colon cancer cells in a dose-dependent manner by inducing G1 phase arrest and apoptosis. Likewise, it suppressed the Jak2/STAT3 and PI3K/AKT/mTOR pathways. Studies on STAT3 transcription regulatory functions showed HSE inhibited the STAT3/DNA binding and transcription promoter activity. Thereby the expression of STAT3 downstream targets VEGF and VEGF-R2 were dropped. Furthermore, HSE treatment suppressed tumor growth and pulmonary metastasis in animal models. Together, these findings suggested that the targeted inhibition of Jak2/STAT3 and PI3K/Akt/mTOR contribute to cancer therapy potential of H. sorghum (HS). Thus, use of sorghum as a dietary supplement has the potential as a nutraceutical to prevent the onset of colon cancer, without any side effects.