A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro

Abstract

Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.

Cardioprotective Effect of Centaurea castriferrei Borbás & Waisb Extract against Doxorubicin-Induced Cardiotoxicity in H9c2 Cells

“…Furthermore, there are no reports on the combined therapy of Centaurea L. plant extracts and chemotherapeutic agents on the various types of cancer. However, many studies that used various plant extracts indicate the enhancement of the effect of DOX on the tested cancer cells [ 47 , 48 , 49 , 50 , 51 ].…”

Cancer microcell initiation and determination

“…DTP cells are characterized as non-genetic anticancer drug-resistant cells, especially against chemotherapy [ 20 , 41 ]. Numerous anticancer drugs, such as paclitaxel and doxorubicin, which were used in this study, as well as methanol, cause cell stress, which creates DNA damage and damage to cellular membranes, interrupting cell homeostasis, and inducing apoptosis [ 42 – 44 ]. The cell membrane after treatment with UV radiation and DOX or PTX becomes permeable [ 43 , 45 ], and it becomes easier to transfect a plasmid DNA into the cells.…”

The Synergism of Natural Compounds and Conventional Therapeutics against Colorectal Cancer Progression and Metastasis

“…Extract of Scabiosa atropurpurea has antioxidant and anticancer properties [91]. Toumia et al [92] discovered that Scabiosa atropurpurea extract increased the cytotoxic effect on adriamycin-resistant Caco-2 tumour cells. RT-qPCR demonstrated that the combination enhanced the mRNA expression of Bax, caspase-3, and p21 while decreasing Bcl-2.…”

“…Combination effects of natural compounds and chemotherapy are shown in Table 2 (Ref. [60,62,[64][65][66][67][68][70][71][72][73][74][75][76]78,79,81,83,84,86,88,90,92,94,96,97,99,101,102,104,105,107,109,112,116]). Research on natural compounds combined with chemotherapy in colon cancer progression and metastases has achieved outstanding results in clinical trials.…”