Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

Abstract

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu) is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro) is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET) was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by down-regulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment.

NLRP3 Inflammasome Activation in Cancer: A Double-Edged Sword

“…Other compounds include Andrographolide ( 89 , 90 ) and Parthenolide ( 96 ), which mainly target NF-κB signaling pathway, but the later was also shown to directly inhibit NLRP3 inflammasome by interfering with its ATPase activity ( 128 ), have also shown promising results in several cancers ( 129 ). For instance, andrographolide was shown to suppress cancer cell proliferation, promote apoptosis in colon cancer ( 91 ), breast cancer ( 92 , 93 ), multiple myeloma ( 94 ), and enhance the antitumor effect of 5-FU in colorectal cancer ( 95 ). Besides, parthenolide have shown positive results in inhibiting tumor cell proliferation in gastric cancer ( 97 ), pancreatic adenocarcinoma ( 98 ), colorectal cancer ( 99 ).…”

Biological properties of andrographolide, an active ingredient of Andrographis Paniculata: a narrative review

“…The pro-apoptotic activity of vincristine and carbo-platinum in HNCC, through increase of ROS, are an example of chemosensitization finally affecting the AKT-p53 pathway (52)(53)(54). Sensitization of colon cancer cells to 5-fluorouracil (5-FU) is mediated by reduction of the p-MET level in the combination treatment (55). Finally, two possible new applications for AG were proposed recently, the first is the preparation of nanofibrous membranes, biodegradable and locally delivering AG for the treatment of cervical cancer (56).…”

Inflammasome inhibitors: promising therapeutic approaches against cancer

“…Among chemotherapeutic drugs, 5-fluorouracil (5-Fu) is the one most commonly used in colorectal cancer. Andrographolide can promote the 5-Fu-induced antitumor effect by repressing the level of phosphorylated cellular-mesenchymal to epithelial transition factor [73]. In colitis-associated cancer, andrographolide inhibits the NLRP3 inflammasome, protecting mice against dextran sulfate sodium-induced colon carcinogenesis [74].…”