Curcumin compound boosts head and neck cancer therapy
The May, 2011 issue of the American Medical Association journal Archives of Otolaryngology -- Head and Neck Surgery published the finding of researchers at the University of Michigan Comprehensive Cancer Center of a benefit for a derivative of curcumin, which occurs in the spice turmeric, in the treatment of head and neck cancer with cisplatin, a platinum-based chemotherapeutic drug. The development of chemotherapy-resistant tumor cells is a major cause of treatment failure in head and neck cancer, resulting in relapse or metastasis.
University of Michigan professor of otolaryngology and pharmacology Thomas Carey, PhD and his associates evaluated the effects of varying doses of cisplatin or cisplatin combined with the curcumin-derived compound FLLL32 on cisplatin-sensitive and cisplatin-resistant cultured head and neck cancer cell lines. FLLL32 added to a low dose of cisplatin was found to be as effective at inducing programmed cell death in cisplatin-resistant cells as four times as much cisplatin alone. The team found that FLLL32 reduced activation of the protein known as signal transducer and activator of transcription 3 (STAT3), which is elevated in approximately 82 percent head and neck cancers and has been associated with cisplatin resistance.
"Typically, when cells become resistant to cisplatin, we have to give increasingly higher doses," explained Dr Carey, who is the codirector of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center. "But this drug is so toxic that patients who survive treatment often experience long-term side effects from the treatment.”
“This work opens the possibility of using lower, less toxic doses of cisplatin to achieve an equivalent or enhanced tumor kill," he remarked.
"The absence of dose-limiting toxic effects seen with curcumin, the compound on which FLLL32 is based, suggests that STAT3 inhibitors may have a clinical role in the future," the authors conclude. "Continued investigation of the JAK/STAT pathway and the design of novel inhibitors, like FLLL32, that are capable of targeting this pathway may herald new therapeutic approaches that enhance or obviate the need for currently used chemotherapeutic agents."
The dose-delivery schedule of chemotherapy drugs can determinate their efficacy in killing cancer cells and the degree of toxicity to the patient. Conventional chemotherapy treatment often uses a maximum tolerated dose (MTD) of chemotherapeutic drugs, typically administered on a schedule that varies from once a week to every 21 days, allowing a period of rest so that healthy tissue has a chance to recover. Unfortunately, while the MTD schedule is convenient for oncologists, allowing them to squeeze more patients each month into their chemotherapy unit, the rest period enables cancer cells to recover and develop survival mechanisms such as new blood vessel growth into the tumor. This means that when the next high dose of chemotherapy is given 7-21 days later, the cancer cells have become more resistant. The administration of the MTD also exposes healthy tissues to more damage.
Some studies indicate that a better approach would be to lower the dose of conventional cytotoxic agents, reschedule their application, and combine chemotherapy drugs with antiangiogenesis agents to effectively interfere with cancer's various growth pathways and inhibit the production of blood vessels (Holland et al. 2000).
Conventional chemotherapy drugs too often show limited efficacy. Yet there is evidence indicating that the cancer cell-killing effects of these drugs can be enhanced if additional compounds are administered to the patient.
One approach is to inhibit the overexpression of receptor sites on cancer cells, which enables these cells to bind to growth factors that allow them to become resistant to the cell-killing effects of the chemotherapy drugs. Cancer cells use these signal transduction pathways as growth vehicles to escape natural regulatory control and also to protect themselves against the cytotoxic effects of cancer drugs. The utilization of these signal transduction inhibitors enhances the potential effect of low(er) dosing of chemotherapeutic drugs.
Another therapeutic target is the endothelial cells that form new blood vessels. The process by which new blood vessels are formed is called angiogenesis, and cancer cells initiate blood vessel proliferation in order to fuel rapid growth (Hanahan et al. 2000). Agents that interfere with the formation of new blood vessels are an important part of a comprehensive treatment strategy.
Soy (genistein) extract is known to inhibit the epidermal growth factor (EGF) receptor via an interference with the TGF-alpha pathway (Bhatia et al. 2001).
Curcumin, an extract of the spice turmeric, is synergistic with genistein and inhibits angiogenic growth signals emitted by tumor cells. Curcumin acts via a different mechanism than genistein to inhibit the EGF receptor but is up to 90% effective in a dose-dependent manner.
Our warnings about radiation were ignored! by Foster Stevens Back in 2002, we urged the public to maintain a personal supply of potassium iodide in case of a nuclear emergency. Here we enlighten readers to a comprehensive nutritional regimen to help protect the entire body in case a radiation emergency occurs in your geographic area. Read the full story
Vindication for Linus Pauling by William Faloon In this report, from the May 2002 edition of Life Extension Magazine®, we detail Nobel laureate physicist Dr. Linus Pauling’s lifelong campaign to ban above ground nuclear testing despite relentless Federal opposition. Read the full story
Reverse skin aging around your eyes by Gary Goldfaden, MD, and Robert Goldfaden The area of thin, delicate skin around the eyes is one of the first places where signs of aging appear. Discover what causes these visible indications of aging and how to reverse them naturally. Read the full story
Reduce stubbornly high triglycerides by Jen Storch A recent study shows that tocotrienols can lower artery-clogging triglycerides by 28%. This is especially relevant for those who have less-than-optimal triglyceride levels even though they take the proper dose of fish oil. Read the full story
Life Extension Mix™ Vegetarian Tablets save time and money by combining the most popular nutrient supplements into one product, eliminating the need to take separate B-complex, vitamins C and E, mineral supplements, and much more that would be required to achieve the same effects.
Life Extension Mix™ Vegetarian Tablets supply the most powerful antioxidants, including water- and fat-soluble vitamin C, vitamin E, and plant extracts that help protect against cellular DNA damage. Other ingredients enhance beneficial DNA methylation patterns, help maintain glycemic control, and help prevent the oxidation of LDL that contributes to the buildup of deposits in the endothelial lining.
Pantothenic Acid Capsules
Pantothenic acid plays a role in the synthesis of hemoglobin, steroid hormones, neurotransmitters, and lipids. It is the most important component of coenzyme-A, which assists in several metabolic pathways and is necessary for the transfer of fats to and from cells. Pantothenic acid is only mildly acidic, but is often available in combination with calcium to neutralize its acidity and increase its storage stability.