Colorectal cancer (CRC) is the most common cancer in the world, beginning in the cell lining of the colon and rectum. 5-fluorouracil (5-FU) is a first-line therapy for colorectal cancer patients. However, the response rate of 5-FU in advanced colorectal cancer patients is only 10 - 15 %, and can fail due to drug resistance. Therefore, the development of a new anticancer compound for improving the response rate or for reversing resistance to 5-FU is urgently needed. Oxymatrine is a major component of Sophora flavescens. Recently, many pharmacological effects have been exhibited. The objectives of the present study were to investigate the anticancer activity of oxymatrine, as well as to potentiate the effect of oxymatrine with 5-FU on cell viability, colony-forming, cell migration, cell invasion, and determined MMP-9 protein expression in SW-620 colorectal cancer cells. The results demonstrated that oxymatrine significantly inhibited the cell viability of SW-620 cells after 24, 48, and 72 h treatments. Oxymatrine and 5-FU interaction was synergistically greater in inhibiting the cell survival of SW-620 cells than 5-FU was alone. Oxymatrine also decreased colony formation, cell migration, and cell invasion through reducing the level of MMP-9 protein in SW-620 cells. These first findings elucidated an efficacious anticancer agent, which is derived from natural sources, which could be used to overcome 5-FU resistance in colorectal cancer, and may be beneficial for patients with colorectal cancer who are treated with 5-FU.
Centella Asiatica has been traditionally used as herbal medicine to treat various disorders, such as ulcers and psoriatic disease. ECa233 is an herbal extract of Centella Asiatica containing madecassoside (46.3 %) and asiaticoside (41.6 %) that shows a highly acceptable safety profile appropriate for drug development and use as an herbal drug for humans. 5-fluorouracil (5-FU) is a chemotherapeutic agent generally known as the first-line chemotherapy for colorectal cancer. Representative combined chemotherapy with 5-FU, namely the FOLFOX regimen (5-FU, leucovorin, oxaliplatin), has been widely used in hospitals and is typically selected as a chemotherapeutic regimen in prescriptions. However, the unresolved problems appearing in clinical situations are the refusal to accept the chemotherapy leading to drug resistance and the severe side effects after being administered intravenously to the entire body. Therefore, the discovery of a novel pure standard agent to enhance the efficacy of 5-FU and overcome this drug resistance still needs to be explored. To assess the pharmacological activity and safety profile of ECa233 is a major goal in cancer drug discovery. ECa233 was evaluated for its anti-cancer, anti-migration, anti-invasive activities and was explored regarding the safety data on normal cells. The results demonstrated that ECa233 effectively inhibited the cell viability, colony forming, and truly inactivated cell migration/invasion through repressive the MMP-9 invasive factor. Pharmacological interaction with 5-FU was synergism in cancer cells and highly safe to normal cell growth. The results suggest that ECa233 could be used as a combinative drug therapy with standard chemotherapy treatment and other medicinal drugs such as a targeted therapy to treat colorectal cancer patients.
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