Chinese Herb/Chemotherapy Interactions in Breast Cancer

Institution: University of California, San Francisco
Investigator(s): Michael Campbell, Ph.D. -
Award Cycle: 2003 (Cycle IX) Grant #: 9WB-0042 Award: $200,000
Award Type: STEP Award
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure



Initial Award Abstract (2003)
Traditional Chinese Medicine (TCM) is a treatment modality that has been used for centuries to treat cancer, prolong life, and increase the quality of life for cancer patients. The lack of evidence-based clinical trials coupled with the proliferation of anecdotal and case report studies of TCM make it an important treatment modality to study. TCM use in the San Francisco Bay Area is widespread and frequently used by our patient population, thus it can be studied using standard research models at our institution. There is a high degree of conformity among TCM practitioners in terms of diagnoses and treatments due to the extensive historically-based documentation of TCM treatment modalities.

We have recently obtained laboratory data on the effects of over 70 Chinese herbal extracts on the growth of breast cancer cells in culture. These herbs have been traditionally prescribed by TCM practitioners for metastatic breast cancer and other cancer patients. Many of these herbal extracts demonstrated significant inhibitory effects in our initial screening. Since many cancer patients who take these herbs also receive conventional chemotherapy, the objective of this project is to determine what kinds of interactions these herbs have with standard chemotherapeutic agents.

Herbs will be prepared as boiled teas, as they are traditionally prepared. Breast cancer cells growing in tissue culture will be treated with individual herbs, chemotherapeutic drugs, or combinations of an herb with a chemotherapeutic drug. After three days of treatment, the cells will be analyzed for growth/death. Growth curves will be generated from these data and comparisons of the curves from individual herbs, drugs, and their combinations will determine whether the herbs act to enhance the effects of the drugs, inhibit their effects, or have no effect. We will then examine the effects of herb/drug combinations that show greater activity than either alone in a mouse model of breast cancer.

Rather than randomly screening thousands of plants for anti-breast cancer activity, we have focused on plants which have been used for hundreds/thousands of years in Chinese medicine. In addition, we are administering these agents as “teas” which is how they are traditionally administered to patients.


Final Report (2005)
Traditional Chinese Medicine (TCM) is a treatment modality that has been used for centuries to treat cancer, prolong life, and increase the quality of life for cancer patients. The lack of evidence-based clinical trials coupled with the proliferation of anecdotal and case report studies of TCM make it an important treatment modality to study. TCM use in the San Francisco Bay Area is widespread and frequently used by our patient population, thus it can be studied using standard research models at our institution. There is a high degree of conformity among TCM practitioners in terms of diagnoses and treatments due to the extensive historically-based documentation of TCM treatment modalities.

We have recently obtained laboratory data on the effects of over 70 Chinese herbal extracts on the growth of breast cancer cells in culture. These herbs have been traditionally prescribed by TCM practitioners for metastatic breast cancer and other cancer patients. Many of these herbal extracts demonstrated significant inhibitory effects in our initial screening. Since many cancer patients who take these herbs also receive conventional chemotherapy, the objective of this project is to determine what kinds of interactions these herbs have with standard chemotherapeutic agents.

The specific aims of this proposal are: (1) To determine the types of interactions (synergistic, additive, antagonistic) between chemotherapeutic drugs and a panel of Chinese medicinal herbs that alone have growth inhibitory activity on cancer cells and (2) to evaluate the anti-tumor effects of herb/drug combinations on the growth of murine mammary tumor cells in vivo.

We have tested aqueous extracts of a panel of 12 Chinese medicinal herbs alone and combined with the chemotherapeutic agent doxorubicin for anti-cancer activity in vitro. Although most of the herbs showed additive activity when administered simultaneously with doxorubicin, a few were antagonistic. We then determined that administration of these herbs prior to or after treatment with doxorubicin (but not at the same time) yielded additive growth inhibitory effects.

One possible mechanism by which the herbs could be enhancing the effects of doxorubicin is by increasing the uptake (or decreasing the efflux) of doxorubicin in the cells. We tested this hypothesis using a fluorescent dye (rhodamine 123) uptake assay and found that one herb, Vaccaria segetalis, enhanced the uptake of rhol23, suggesting that its activity in combination with doxorubicin may be due to its ability to enhance uptake of the drug into the cancer cells. None of the other herbs showed significant effects on rho 123 uptake.

We have also demonstrated that several herbs with growth inhibitory effects on a drug sensitive human breast cancer cell line (MCF-7) were also effective against a drug resistant cell line (NCl/ADR-RES). These results suggest that the active compounds in these herbs are not affected by the multidrug resistance efflux system and that they may prove useful for the treatment of drug resistant breast cancer.

Finally, we have shown that V. segetalis, A. asphodeloides, or S. barbata antagonize the anticancer activity of doxorubicin in vivo when administered at the same time. These results are similar to the in vitro results with these three herbs. In contrast, these herbs acted additively when administered sequentially with doxorubicin in vitro. Thus, in vivo studies evaluating the effects of sequential administration of these herbs plus doxorubicin are ongoing.


Symposium Abstract (2005)
Traditional Chinese Medicine (TCM) is a treatment modality that has been used for centuries to treat cancer, prolong life, and increase the quality of life for cancer patients. TCM use in the San Francisco Bay Area is widespread and frequently sought out by our patient population. There is a high degree of conformity among TCM practitioners in terms of diagnoses and treatments due to the extensive historically-based documentation of TCM treatment modalities. However, the lack of evidence-based clinical trials coupled with the proliferation of anecdotal and case report studies of TCM make it an important treatment modality to study.

We have recently obtained laboratory data on the effects of over 70 Chinese herbal extracts on the growth of breast cancer cells in culture. These herbs have been traditionally prescribed by TCM practitioners for metastatic breast cancer and other cancer patients. Many of these herbal extracts demonstrated significant inhibitory effects in our initial screening. Since many cancer patients who take these herbs also receive conventional chemotherapy, the objective of this project is to determine what kinds of interactions these herbs have with standard chemotherapeutic agents.

We have evaluated the anti-tumor effects of a panel of Chinese medicinal herbs in combination with doxorubicin chemotherapy on breast cancer cells in culture and in a mouse model of breast cancer. Many of the herbs when administered simultaneously with chemotherapy demonstrated antagonistic interactions, both in culture and in the mouse model system. However, we found that some of these herbs, when administered either before or after chemotherapy, demonstrated additive effects.

These results suggest that maximum cytotoxic effects can be obtained with sequential administration, but not simultaneous administration of herbs and doxorubicin chemotherapy. These findings may have important clinical implications for the use of Chinese medicinal herbs in conjunction with standard chemotherapeutic agents.