Effects of Turmeric Compounds on Cell Cycle Proteins Involved in Cancer

Cells reproduce (or proliferate) by making copies of themselves. Different proteins are responsible for moving a cell through the various phases of cell cycle growth and replication. ^(vi.3)

Phase Diagram - Cell Cycle

Turmeric's Curcumin Compounds Help Regulate Cell Cycle Proteins

Studies show that turmeric compounds such as curcumin and its derivatives (e.g., HBC) inhibit or stimulate proteins that stop cancer cells from growing. Whether directly or indirectly, turmeric compounds block or allow cell cycle proteins such as cyclins and Ki-67, depending on the type of cancer. ^(vi.36, 42)

Some examples of how the turmeric compound curcumin affects the same cell cycle factor differently depending on the cancer include:

• Cyclin D1. In cancers that produce too much cyclin D1, the turmeric compound curcumin does not directly inhibit the protein's effects. It allows the cancer cell to move to the G2 phase of the cell cycle, where it then undergoes orderly, non-inflammatory cell death. This type of cell death is known as apoptosis, and it helps get rid of defective cells so they don't replicate mutated DNA. ^{(vi.3, 30, 42, 104-106)}

  However, with some cancers curcumin will activate transcription factors and cofactors (such as PPAR-γ and BTG) that suppress cyclin D1. This stops cancer cells from progressing by arresting them in a cell cycle phase before it can replicate. Arresting cancer cells in certain phases also makes them more vulnerable to different chemotherapy and radiation treatments. ^{(vi.3, 30, 42, 104-106)}

• Cyclin B. In some cancers, curcumin blocks enzymes that activate cyclin B in the mitosis (M) phase of the cell cycle. This arrests the cancer cell in that phase. But in others, such as pancreatic cancer cell lines, curcumin increases cyclin B to induce a mitotic catastrophe type of cell death. ^{(vi.3, 30, 42, 104-106)}

Even in situations where the cancer cell is already in the replication (S) phase of the cell cycle, turmeric's curcumin compounds can block it from generating a copy of its mutated DNA for new cancer cells. It does so by suppressing factors that promote tumor cell growth and invasion: ^{(vi.42, 104)}

• Inflammatory enzymes
• Protein kinases
• Transcription factors
• Cell survival/proliferation oncogenes

Curcumin Also Helps Regulate Ki-67 Proteins

Research demonstrates that high levels of Ki-67 (a protein located in the nucleus of cells) are associated with poor prognosis in many types of tumors, including melanoma and breast cancer. Although its exact cell-cycle function is still unknown, Ki-67 levels rise significantly when tumor cells are actively dividing and replicating. Suppressing Ki-67 stops cancer cells from proliferating. ^{(vi.6, 9, 20, 107-108)}

In normal cells (even those that do proliferate, such as skin cells) Ki-67 levels are absent or very low. They progressively rise in pre-cancerous lesions to even higher levels in full-blown malignancy. The turmeric compound curcumin has been shown to inhibit Ki-67 in numerous cancers (e.g., breast cancer, colorectal cancer, glioblastoma brain cancer, skin cancer, multiple myeloma, and bladder cancer). ^{(vi.6, 9, 20, 107-108)}

Other Active Turmeric Compounds

Other compounds in turmeric that block the production and effects of cell cycle proteins include:

• ALPHA-TURMERONE (in breast cancer) ^(vi.91)
• EUGENOL (cyclin D1) ^(vi.74, 77)
• FARNESOL (cyclin A and cyclin B1 in pancreatic cancer) ^(vi.109-111)
• GERANIOL (in pancreatic cancer) ^{(vi.109, 112)}
• MYRICETIN (cyclin D1) ^(vi.77, 79)
• QUERCETIN (cyclin D1) ^(vi.56, 79)