Compound Opening Arrow Mixture exerts anti-tumor effects in a mouse model of breast cancer

Abstract

Compound Opening Arrow Mixture (COAM) has demonstrated therapeutic effects in patients with breast cancer. We explored the underlying molecular mechanisms of COAM using a mouse model of breast cancer. Luciferase-labeled 4T1-Luc2 cells were inoculated into the breast pad of BALB/c-nu mice, which were divided into model group (saline), COAM (6 g/ml high-dose, 3 g/ml medium-dose, and 1.5 g/ml low-dose) groups, and low-molecular-weight heparin (LMWH, 1500 U/Kg) group. The number and distribution of 4T1-luc2 tumors were measured by an in vivo imaging system. Tumor cell apoptosis was measured through TUNEL and quantitating the expression of Caspase-3 mRNA and protein. Compared with the model group, in vivo tumor growth was lower in the LMWH- and COAM-treated groups. Tumor apoptosis was time-dependent and dose-dependent, as shown by a higher TUNEL apoptotic index and higher Caspase-3 mRNA and Caspase-3/cleaved-Caspase-3 proteins levels on the 14th day than the 7th day. The COAM high-dose group had the highest apoptotic index and the most activation of Caspase-3. Collectively, COAM significantly inhibits the growth of 4T1-luc2 breast cancer in mice and induces tumor apoptosis by activating Caspase-3, which provides a preliminary explanation of therapeutic effects of COAM.

East Wind, West Wind: Toward the modernization of traditional Chinese medicine

“…The molecular mechanisms by which these preparations act are slowly emerging. For instance, COAM (compound opening arrow mixture) has shown anti-tumor effect in a mouse model of breast cancer by activating caspase 3 ( Zhou et al, 2020b ); the beneficial effects of LongSengZhi (LSZ) capsule in cardiovascular disease and heart failure can be attributed to the reduction in the production of reactive oxygen species and inhibition of both inflammation and activation of platelets and endothelial cells ( Li et al, 2019 ; Xu et al, 2020 ), and the flavonoid extract from Dracocephalum moldavica (which includes apigenin, luteolin, acacetin, gardenin B, serophulein, salvigenin, isorhamnetin, tilianin, agastachoside and kaempferol) downregulates β-secretase and thus decreases insoluble amyloid β deposition, improving memory capacity and inhibiting neurodegeneration ( Liu Q. S. et al, 2018 ; Table 1 ). Others, such as Qishen Yiqi Dripping Pills (QSYQ), Fo Shou San (FSS), and Dang gui shao yao san (DGSYS) are much better characterized.…”

“…Other preparations have a well-established record of traditional use, and, in some, their mechanism of action has started to be unraveled, although no active compounds have been isolated. In cancer, and to cite only a few examples, COAM (a herbal complex mixture with many plants) has anti-tumor effect in a mouse model of breast cancer by activating caspase 3 ( Zhou et al, 2020b ); Huaier, an officinal fungus, effective in breast cancer treatment ( Yao et al, 2020 ), suppresses breast cancer progression via linc00339/miR-4656/CSNK2B signaling pathway ( Wang W. et al, 2019 ) and sensitizes breast cancer cells to radiotherapy by interfering with the homologous recombination pathway and DNA repair by downregulating RAD51 ( Ding et al, 2016 ); the anti-tumor activity of Ruanjian Sanjie (RJSJ) decoction has been attributed to suppression of the anti-apoptotic proteins BCL2 and survivin, leading to the activation of caspases-3/7 and caspase-9; importantly, administration of RJSJ in combination with doxorubicin is more effective and safer than the chemotherapeutic treatment alone in breast cancer xenografts ( Zhao et al, 2017 ; Table 1 ). Doxorubicin is widely used as a chemotherapeutic in cancer treatment although it has severe and irreversible cardiotoxicity.…”

Ocimum sanctum Linn. Ethanolic extract promotes an antiproliferative and apoptosis activity in MCF-7 and T47D breast cancer cell lines mediated by upregulation of ROS/RNS, Caspase 9, and Caspase 3: an in silico and in vitro study

“…Therefore, new strategies to effectively control cancer growth are urgently needed. 6 While modern and conventional medicine has been used as the main medicine for cancer treatment, traditional herbal medicine has been commonly used as a complementary and alternative strategy in several countries. 7 Plants have long been known for their therapeutic properties.…”