Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer

Abstract

Aim: The aim of this study was to test for the influence of ascorbic acid on tumorigenicity and metastases of implanted PAIII prostate cancer adenocarcinoma cells in syngeneic LW rats.

Materials and methods: Hormone-refractory prostate cancer PAIII cells were implanted subcutaneously into immunologically intact, Lobund-Wistar (LW) rats. Intraperitoneal pharmacological doses of ascorbic acid were administered each day for the ensuing 30 days. On the 40th day, animals were sacrificed. Local tumor weights were measured, and metastases were counted.

Results: At the end of the 40 day experimental period, the primary tumors were found to be significantly reduced in weight (p=0.026). In addition, sub-pleural lung metastases were even more profoundly reduced in number and size (p=0.009). Grossly enlarged ipsilateral lymph node metastases declined from 7 of 15 rats to 1 of 15 rats.

Conclusion: Pharmacological doses of ascorbic acid suppress tumor growth and metastases in hormone-refractory prostate cancer.

Figure 1.

Images of primary PAIII tumor, axillary lymph node, and lung metastases in LW rat. a: Gross image of LW rat implanted with PAIII tumor cells. Primary PAIII tumor (labeled arrow) is shown for a control rat inoculated with 10⁶ tumor cells. An enlarged, ipsilateral axillary lymph node is shown (see labeled arrow). Sub-pleural metastases are shown (see labeled thin arrow). b: Sub-pleural lung metastases. Lung metastases are grossly shown on rat lung surface. Large and small metastases are seen. The data in this paper are based on total sub-pleural metastases observed using ×5 magnification.

Figure 2.

Influence of ascorbate on primary tumor weight and number of lung metastases. a: Influence of ascorbate treatment on primary tumor weight. Fifteen LW rats were treated with 10⁶ PAIII cells, as described. Fifteen other rats were inoculated with the same number of PAIII cells, but also treated with ascorbate (4 g/kg), as described. After 40 days, rats were sacrificed and primary tumors dissected out for measurement of weight. The difference in weight between treated and untreated rats is significant (*p=0.026). b: Influence of ascorbate treatment on number of lung metastases. Lungs from the animals analyzed in Part a were fixed in Bouin’s Fixative, and the total number of metastases counted. The difference in numbers of lung metastases in the two conditions is significant (#p=0.009).

Figure 3.

Receiver operating condition (ROC) curves for ascorbate effects on primary tumor weight and number of lung metastases. a: ROC curve for ascorbate effects on primary tumor weight. Area under the curve (AUC) is 0.75. A perfect discriminating cut-off point would have a value of 1.0. b: ROC curve for ascorbate effects on the number of lung metastases. Area under the curve (AUC) is 0.74. A perfect discriminating cut-off point would have a value of 1.0.

Figure 4.

Ascorbate effects on the relationship between primary tumor weight and number of lung metastases. Data relating tumor weight to metastatic number in the absence of ascorbate treatment are shown in solid diamonds. The R² value is only ∼0.04, indicating essentially random distribution. Data relating tumor weight to metastatic number in the presence of ascorbate treatment are shown in solid squares. The R2 value is ca. 0.5, indicating a somewhat linear relationship. The vertical intercept is ca. −4.7, indicating a discrete lag between primary tumor weight and metastatic number.