Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene) and retinoids (9-cis, 13-cis and all-trans retinoic acid) on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+) MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM) didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%, p<0.01 and 40.67 +/- 5.62%, p<0.01) in comparison to the docetaxel only group. The above-mentioned observations were also confirmed with the use of the immunohistochemical investigations. Among the examined vitamin A family compounds, the simultaneous application of beta-carotene (0.1 microM) and docetaxel (0.2 microM) resulted in a statistically significant reduction in the percentage of proliferating cells (40.25 +/- 14.62%, p<0.01). Lycopene (0.1 microM), which stimulates the growth of breast cancer cells in a 24-hour culture, had an inhibitory effect (42.97 +/- 9.58%, p<0.01) when combined with docetaxel (0.2 microM). Although, beta-carotene and lycopene belong to the different chemical groups, they surprisingly had a similar inhibitory influence on both growth and proliferation of MCF-7 breast cancer cells when combined with docetaxel. The application of docetaxel either with beta-carotene or lycopene had comparable inhibitory effect on breast cells growth and proliferation as tamoxifen. Therefore, it may suggest a possible important role of these carotenoids in the breast cancer therapy in women especially when docetaxel is applied.
An attempt has been made to identify the carotenoids present in the tissue of neoplastic tumors and the surrounding fatty tissue taken from women with histologically diagnosed cancer (ca ductale infiltrans, G2,G3; n=20) and those with benign changes (fibroadenoma, n=20). Carotenoid pigments were isolated using column and thin-layer chromatography. Prior to chromatography, the material was homogenized with acetone under nitrogen in dark glass bottles and the extracts kept in a refrigerator until analyzed. In the present study, we isolated 13 carotenoids belonging to provitamin A and nonprovitamin A carotenoids. The total content of carotenoids in microg/g of tissue was slightly lower in cancers and the surrounding fatty tissues in comparison to benign changes, but in general it was higher in the fatty tissue surrounding the tumors, irrespective of their histological structure (the mean values for cancers 20.433+/-10.64 vs fatty tissue 25.361+/-12.025, p<0.01; and the mean values for benign changes 22.889+/-12.011 vs fatty tissue 27.021+/-13.180, p<0.01). Epoxide carotenoids - lutein epoxide and violaxanthin, were predominant in fatty tissue, both in malignant and benign changes; epoxide carotenoids - mutatoxanthin and lutein epoxide and other carotenoids such as zeaxanthin, canthaxanthin, lutein and neoxanthin were predominant in neoplastic material. Beta carotene and lutein epoxide were found in all samples, alpha carotene was found in 50% of them. Antheraxanthin was present in fatty tissue only. Beta carotene, the main provitamin A carotenoid, content in the material examined ranged from 2.43 to 4.33% in tumor tissue and in fatty tissue surrounding the tumors it was twice as higs. Such carotenoids as 3'-lutein, canthaxanthin and astaxanthin were sporadic. No reoccurring carotenoid "sequences" were found despite the same histopathological diagnosis. No relationship was found between the neoplasm histopatological grade, lesion diameter and the occurrence of specific carotenoids.
Endometrioid carcinoma represents approximately 10% of cases of the malignant ovarian epithelial tumors. According to literature, the vitamin A (carotenoids and retinoids) plays an essential role in cell proliferation, differentiation and apoptosis in both normal and neoplastic ovarian tissues. Apart from that, the retinoids alter a cytotoxic effect of chemiotherapeutics, i.e. docetaxel, on ovarian cancer cell lines. Retinoids act on cancer cells throughout different mechanism than taxanes, so they may be the potential candidates for the new treatment strategies of ovarian cancer. The aim of the study was to determine the effects of vitamin A family compounds (retinol, beta-carotene, lycopene, all-trans -, 9-cis - and 13-cis retinoic acid) on the growth and proliferation of CRL-11731 endometrioid ovary cancer cell line and on docetaxel and estradiol activity in this culture. The assay was based on [3H] thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in CRL-11731 cells were also studied. Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner. Only the concentration of 100 muM of docetaxel inhibited incorporation [3H] thymidine into CRL-11731 cancer cells. Retinol (33.4%+/-8.5), carotenoids (beta-carotene 20 muM 4.7%+/-2.9, 50 muM 2.2%+/-0.9; lycopene 10 muM 7.6%+/-0.8, 20 muM 5.2%+/-2.5, 50 muM 2.9%+/-1.2), and 13-cis retinoic acid (19.7%+/-2.2) combined with docetaxel (100 muM) significantly decreased the percentage of proliferating cells (p<0.0001). The antiproliferative action of lycopene alone and in combination with docetaxel was also confirmed in immunohistochemical examination (decreased the percentage of PCNA and Ki67 positive cells). Also retinol (10 muM) and lycopene (20 and 50 muM) combined with estradiol (0.01 muM) statistically decreased the percentage of proliferating cells compared to the control (p<0.0001) and estradiol (p<0.01, p<0.0001) group (63.5%+/-14.8, 61.0%+/-20.6, 15.0%+/-5.5 respectively). In our experiments, the compounds tested induced an apoptotic effect. Docetaxel and estradiol increased the percentage of apoptotic cells (71% apoptotic cells after administration of 10 muM all-trans retinoic acid combined with 0.01 muM estradiol, p<0.0001). beta-carotene, lycopene and all-trans retinoic acid alone and in combination with docetaxel were found to influence the expression of bcl-2 and p53 antigen in the cells examined. The results of our study justified an important role of vitamin A in the pathophysiology of the ovarian endometrioid cancer.
Abstract Reverse‐phase high‐performance liquid chromato‐graphy, column and thin‐layer chromatography re‐vealed the presence of following carotenoids in the thalli of 10 species (14 specimens) of lichens from the Colombian Andes: β‐carotene, β‐cryptoxanthin, zeaxanthin, lutein, calthaxanthin, caloxanthin, 3′‐hydroxyechinenone, canthaxanthin, fritschiellaxanthin, astaxanthin, antheraxanthin, violaxanthin, neoxanthin, mutatoxanthin and capsochrome. The total content of carotenoids ranged from 18.41 μg g −1 ( Stereocaulon ramulosum ) to 45.78 μg g −1 ( Thamnolia vermicularis , no. 3) dry mass.