Abstract
Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, Sanguisorba officinalis L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world.According to the cancer statistics in 2019, CRC is the second most common cancer in males and the third in females [1]
The results showed that the acid β-d-glucopyranosyl ester (AGE) (Figure 1A) predominantly suppressed the cell proliferation in dose-dependence (Figure 1C,D)
Improved treatment strategies have been applied in clinics, there is an urgent need to find novel and effective agents for CRC treatment due to the occurrence of side effects and the emergence of drug resistance
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. According to the cancer statistics in 2019, CRC is the second most common cancer in males and the third in females [1]. Surgery and chemotherapy are two main prescriptions for CRC treatment. 5-fluorouracil (5-FU) remains the mainstay for chemotherapy of CRC [2,3]. More and more patients have developed drug resistance due to. 5-FU-based chemotherapies [4], leading to failure in CRC treatment. It is of prominent importance to develop novel agents to treat CRC effectively. An attractive strategy is to find bioactive compounds from natural plants or Chinese medicine
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