Table 1.
(A) Selective natural compounds used in breast cancer therapy; (B) selective preclinical and clinical studies of novel agents for breast cancer prevention.
| (A) SELECTIVE NATURAL COMPOUNDS USED IN BREAST CANCER THERAPY | ||||
|---|---|---|---|---|
| Compound | Source | Studies | Effect | Reference |
| Flavonoid | ||||
| Honokiol | Magnolia officinalis and Magnolia grandiflora | ER+ MCF-7, MDA-MB-231 ER− breast cancer | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant | (52) |
| Magnolol | Magnolia officinalis and Magnolia obovata | MDA-MB-231 | It causes cell cycle arrest, apoptosis, and acts as antiproliferative agent | (53) |
| Sesquiterpenes | ||||
| Costunolide | Inula helenium, Saussurea lappa, and Magnolia grandiflora | MCF-7, MDA-MB-231 | It arrests cell cycle leads to apoptosis in cancer cells, and acts as antioxidant | (54) |
| Parthenolide | Tanacetum parthenium, Tanacetum vulgare, Centaurea ainetensis, Tanacetum larvatum, and Helianthus annuus | MCF-7, MDA-MB-231 | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant. Cytotoxic | (55) |
| Diterpenoids | ||||
| Pseudolaric acid B | Pseudolarix kaempferi | MCF-7, MDA-MB-231 | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant | (56) |
| Oridonin | Isodon rubescens | MCF-7, MDA-MB-231 | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant. Autophagic agent | (57) |
| Polyphenolic | ||||
| Wedelolactone | Eclipta alba, Wedelia calandulaceae, and Wedelia chinensis | MDA-MB-231,468 | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant | (58) |
| Alkaloids | ||||
| Evodiamine | Evodia rutaecarpa | MCF-7 | It arrests cell cycle, leads to apoptosis in cancer cells, and acts as antioxidant, antimetastatic, and anticarcinogenesis | (59) |
| (B) SELECTIVE PRECLINICAL AND CLINICAL STUDIES OF NOVEL AGENTS FOR BREAST CANCER PREVENTION | ||||
| Drugs/agents | Studies: in vitro, in vivo, trials | Effect on breast cancer | Source | Reference |
| Beta-lactam | MCF-7 and MDA MB-231 breast cancer cells, xenograft mouse model | It inhibits proliferation of breast cancer cells and tumor growth in mouse model. Beta lactamase linked affinity reagents based on cancer cell fusion peptides can be used directly in targeted enzyme prodrug development in cancer | β-lactam ring are group of antibiotics such as penicillins, carbapenems, and monobactams | (60–63) |
| Triphenylethylenes | ER-positive MCF-7 and the ER-negative breast cancer cell line T47D, BALB/c athymic mice | It is used for breast cancer treatment, examples are tamoxifen, idoxifene, and toremifene. Tamoxifen is used in ER+ breast cancer, its dose 20 mg/day is optimized in ongoing clinical trials to reduce toxicity | Non-steroidal antiestrogens | (64) |
| Letrozole | MCF-7 breast cancer cells, MCF-7Ca tumor xenograft models and BALB/c athymic nude mice BIG 1-98 study group clinical trial compared letrozole and tamoxifen drug in breast cancer patients |
It is used in local or advanced breast cancer having hormone receptor positive. It is used in combination with tamoxifen with improved overall survival | Non-steroidal aromatase inhibitor | (65, 66) |
| Anastrozole | Murine breast cancer cells (4T1) in female BALB/c mice ATAC clinical trial compared anastrozole and tamoxifen for treatment of breast cancer |
The combination trial of ATAC showed that it has more efficiency and less side effects than tamoxifen and can be used as initial treatment for postmenopausal women with ER+ breast cancer | Non-steroidal aromatase inhibitor | (67) |
| Cyclosporin A | Multidrug-resistant human breast cancer cells MCF-7-adriamycin-resistant (AdrR), female athymic nude BALB/c mice | It lowers levels of glucosylceramide in multidrug-resistant cells which are given tamoxifen. It functions as a chemoresponsive agent. Pharmacokinetics of docetaxel in combination of CsA showed active and safer use for treating advanced breast cancer in Phase II study | It is an immunosuppressant drug | (68, 69) |
| Verapamil | BALB/c mouse murine breast cancer cells (4T1-R) | It inhibits multi drug resistance rendering cells sensitive to chemotherapy at an optimal concentration of 6 and 1–2M | It functions as an L-type calcium blocker from group of phenylalkylamine | (70, 71) |
| Suramin | MDA-MB-231 cells, xenografted human, athymic mice | The drug binds to TGF, EGFR, FGF, PDGF, and IGF causing impaired growth of cell and is used for breast cancer treatment. In combination with paclitaxel, it is effective and non-cytotoxic in metastatic breast cancer at 10 and 50 μmol/l concentrations in phase I and II trials | It functions as an antagonist of P2 receptors which are ATP-stimulated G protein-coupled receptors | (72, 73) |
| Flaxseed | MCF-7 breast cancer cells, ovariectomized mice, nude mice | It inhibits the growth of human estrogen-dependent breast cancer in athymic mice, and it enhances the inhibitory effect of tamoxifen. Dietary flaxseed reduces tumor growth in breast cancer and is less expensive and available | Flaxseed (FS) is rich in mammalian lignan precursors and α-linolenic acid, which have anticancer effects | (74, 75) |
| Plumbagin | Human breast cancer cell MDA-MB-23, female BALB/c mice | Plumbagin reduces cancer cell growth and osteoclast formation in the bone of mice | It was isolated form plant plumbago | (76) |
EGFR, epidermal growth factor; TGF, transforming growth factors alpha and beta; FGF, fibroblast growth factors; PDGF, platelet-derived growth factor; IGF, insulin-like growth factors; ATAC, anastrozole, tamoxifen combination trial.