Abstract
Cynanchum paniculatum (Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(−) PR(−)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(−)) in a 24 h scratch assay. Our data suggested that ER(−) PR(−) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(−) cells, and this correlated with MMP-2 regulation. The migration of ER(−) PR(−) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.
Highlights
Cynanchum paniculatum (Bge.) Kitag. (CP) belongs to the genus of Cynanchum, a genus of about 300 species including some swallow-worts, and the family Apocynaceae. ey have slender and rigid stems which can grow about 1 meter and the roots are densely fibrous. e root and stem were traditionally used in Chinese medicine for symptoms including pain, arthritis, itching, swelling, and blood smoothing [1].e 992 C.E. classical Chinese medicine book “Taiping Shenghui Fang” described the usage of Shu Changching (i.e., Cynanchum paniculatum (Bge.) Kitag.) for curing heart ache and malicious ulcer, which indicated breast cancer
When they were treated with 5 mg/ml, which is higher than the LC50 of all the cells, MCF-7 and ZR-75-1 cells (both estrogen receptor (ER)(+) progesterone receptor (PR)(+)), demonstrated about 40–50% survival, while MDA-MB-231 and SK-Br-3 (both ER(− ) PR(− )), demonstrated only about 10% survival
Cytotoxicity studies clearly showed that ER(-) PR(-) cells are more sensitive to the CP treatment in terms of direct cytotoxicity. e LC50 of these cells are in the increasing order MDA-MB-231
Summary
E 992 C.E. classical Chinese medicine book “Taiping Shenghui Fang” (the Taiping Holy Prescriptions for Universal Relief ) described the usage of Shu Changching (i.e., Cynanchum paniculatum (Bge.) Kitag.) for curing heart ache and malicious ulcer, which indicated breast cancer. Ese patients are generally younger and show a faster progression of the tumor which makes it very difficult to treat them [8]. For these patients, other types of molecular target drug such as antiangiogenesis or immune therapy drug targeting the Tcell checkpoint provide satisfactory results, the need for new chemical compounds that could act on this specific type of cancer still remains unattended [8, 9]. We intended to test whether CP extract could inhibit the proliferation of MDAMB-231 cells (along with other breast cancer cells with different genetic variants) and deduce the mechanism of cytotoxicity
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