The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy

Abstract

Abstract:Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibits growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells, and may have potential as a chemotherapy or radiotherapy sensitizer in colorectal cancer treatment.

Traditional Chinese medicine Danggui Buxue Tang inhibits colorectal cancer growth through induction of autophagic cell death

“…In our previous study, we determined that the amount of active ingredient in 2.6 g DBT decoction was equal to 0.3 g DBT-PD [ 21 ]. We evaluated the antitumor effect of both DBT and DBT-PD, and found that both DBT and DBT-PD inhibited the growth of colorectal adenocarcinoma in vivo (Figure 1 ).…”

“…In our previous publication, the treatment of 10 mg/mL DBT-PD inhibited the growth of CT26 adenocarcinoma cells and sensitized the cells to chemoradiotherapeutic effects [ 21 ]. The mechanism of DBT-PD-induced CT26 cell death was found to be autophagy-associated.…”

“…The index components astragaloside IV and ferulic acid were detected and quantitated in our previous study. However, purified astragaloside IV (3.126 μg/mL) and ferulic acid (0.014 μg/mL) in amounts equivalent to that contained in 10 mg/mL DBT-PD had no significant growth inhibitory effect [ 21 ]. DBT is a Chinese herbal formula that has been traditionally used to treat menstrual anemia.…”

“…Concurrent treatment of CT26 cells with DBT-PD and 5-fluorouracil (5-FU) markedly inhibited cell growth with a combination index (CI) of 0.42 after 72 h. Moreover, DBT-PD sensitized colorectal cancer cells to radiotherapy and concurrent chemoradiotherapy. This indicated that DBT could serve as a chemoradiosensitizer in colorectal cancer treatment [ 21 ]. The essential components of DBT that inhibit tumor growth should be purified and investigated further.…”

“…Other pharmacological activities, such as an antifibrotic effect in rat lung [ 18 ], a decrease in angiogenesis [ 19 ], and a reduction of oxidative stress in rat liver fibrosis [ 20 ], have also been reported. We have previously reported that DBT was a chemoradiotherapy sensitizer with antineoplastic effects in CT26 cancer cells, particularly the polysaccharide-depleted fraction (DBT-PD) [ 21 ]. Therefore, DBT may be considered a potential new therapeutic option with a novel mechanism for the treatment of CRC.…”