A new study has made an important step forward in demonstrating how andrographis (Andrographis paniculata) works to help people with colorectal (CRC) cancer.
One of the biggest challenges with CRC is that many cases do not respond well to the standard treatment with the chemotherapy drug, 5-flurouracil (5-FU). In fact, up to 60% of cancer patients develop chemoresistance.
Chemotherapy drugs are already toxic to the cancer and to the patient, so there’s only so far that treatment can go before it becomes too dangerous to pursue further. So when cancer cells are resistant, there appears to be few options. Fortunately, this research has found that andrographis, an Ayurvedic herb with a long history of use, has the potential to dramatically improve cancer treatment.
In this study, researchers looked at cellular activity and also used a process called xenografting, where human cancers are grown in mice.
In the experimental models of colorectal cancer using cell samples and xenografted human tumors in this study, the andrographis extract (EP80) overcame 5-FU resistance, and reduced 5-FU resistant tumor cells, in part, by inhibiting the DKK1 pathway. And, perhaps even more impressively, andrographis dramatically reduced tumor growth on its own as well by stopping the mechanisms that can lead to further cancer cell formation. Combined treatment with both andrographis and 5-FU had a synergistic effect on tumor inhibition, showing that the two could be used together for a potentially much higher treatment success rate.
Zhao Y, Wang C, Goel A. Andrographis overcomes 5-fluorouracil associated chemoresistance through inhibition of DKK1 in colorectal cancer. Carcinogenesis. 2021 Apr 5:bgab027.
Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the US. 5-fluorouracil (5FU)-based chemotherapeutic drug remains a mainstay of CRC treatment. Unfortunately, ~50-60% of patients eventually develop resistance to 5FU, leading to poor survival outcomes. Our previous work revealed that andrographis enhanced 5FU-induced anti-cancer activity, but the underlying mechanistic understanding largely remains unclear. In this study, we first established 5FU resistant (5FUR) CRC cells and observed that combined treatment with andrographis-5FU in 5FUR cells exhibited superior effect on cell viability, proliferation and colony formation capacity compared to individual treatments (p<0.001). To identify key genes and pathways responsible for 5FU resistance, we analyzed genome-wide transcriptomic profiling data from CRC patients who either responded or did not respond to 5FU. Among a panel of differentially expressed genes, DKK1 overexpression was a critical event for 5FU resistance. Moreover, andrographis significantly downregulated 5FU-induced DKK1 overexpression, accompanied with enhanced anti-tumor effects by abrogating downstream Akt-phosphorylation. In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (p<0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.
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