The efficacy of Chinese herbal medicine as an adjunctive therapy for colorectal cancer

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

Section: Introductionmentioning

confidence: 99%

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

Environmental Toxicology

“…In addition, studies investigating the efficacy and safety of novel neoadjuvant therapy in CRC patients are ongoing 4–7 . Chinese herbal medicine has been reported as an adjuvant strategy to enhance the efficacy of chemotherapy and targeted therapy against CRC while alleviating adverse reactions 8,9 …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7] Chinese herbal medicine has been reported as an adjuvant strategy to enhance the efficacy of chemotherapy and targeted therapy against CRC while alleviating adverse reactions. 8,9 The combination of Huangci Granule, the Chinese herbal medicine formula, with chemotherapy and anti-epidermal growth factor receptor (EGFR) or anti-vascular endothelial growth factor (VEGF) monoclonal antibody improved progression-free survival and quality of life in metastatic CRC patients. 9 As demonstrated by cell and animal models, natural compounds isolated from Chinese herbal medicines downregulate the growth of CRC by apoptosis, induction of cell cycle arrest, and disruption of oncogenic signal transduction.…”

mentioning

confidence: 99%

Amentoflavone induces caspase‐dependent/−independent apoptosis and dysregulates cyclin‐dependent kinase‐mediated cell cycle in colorectal cancer in vitro and in vivo

Lin

et al. 2023

Colorectal cancer (CRC) is recognized as the third most common malignancy and the second most deadly in highly developed countries. Although the treatment of CRC has improved in the past decade, the mortality rate of CRC is still increasing. Amentoflavone, one of the flavonoids detected in medical plants, is reported to possess potential anticancer properties in various cancers. However, its role in CRC has not been studied. This study aimed to investigate the role and underlying mechanism of amentoflavone on CRC in vitro and in vivo. We identified the cytotoxicity, apoptosis effect, cell cycle alteration, DNA damage induction and tumor progression inhibition of amentoflavone in HT‐29 model by using MTT assay, flow cytometry, immunofluorescence (IF) staining, Western blotting and animal experiments. Amentoflavone induced cytotoxicity is caused by triggering G1 arrest, DNA damage and apoptosis in HT‐29 cells. The expression of cyclin D1, CDK4 and CDK6 was decreased by amentoflavone; in contrast, the phosphorylation of ATM and CHK2 and the expression of p21 and p27 were increased. The apoptosis induction of amentoflavone in CRC is not only caspase‐dependent but also increases EndoG and AIF nuclear translocation in a caspase‐independent manner. Importantly, the apoptosis induction of amentoflavone is not affected by the activity of p53 in CRC. Amentoflavone suppressed the progression of CRC by initiating G1 arrest and ATM/CHK2‐mediated DNA damage‐responsive, caspase‐dependent/independent apoptotic effects. We uncovered a novel tumor‐inhibitory role of amentoflavone in CRC that is not associated with p53 activity, which may serve as a potential treatment for CRC.

“…Network meta-analysis (NMA), which synthesizes evidence from direct and indirect comparisons, is therefore needed to determine the best available treatments. 9 Meta-analysis of Chinese herbal medicine 10 and Chinese herbal injections 11 as an adjuvant therapy for CRC have been reported. However, to the best of our knowledge, the NMA of OCPM combined with chemotherapy has not been involved.…”

Section: Introductionmentioning

confidence: 99%

Oral Chinese Patent Medicine Combined With Oxaliplatin-Based Chemotherapy Regimen for the Treatment of Colorectal Cancer: A Network Meta-Analysis

Tang

Zhai

et al. 2021

Integr Cancer Ther

Objective: To access the comparative effectiveness and safety of different oral Chinese patent medicine (OCPM) versus oxaliplatin-based chemotherapy regimen (C) alone for colorectal cancer (CRC) through network meta-analysis (NMA). Methods: Several electronic databases were searched for randomized controlled trials (RCTs) concentrated on the use of OCPM to treat CRC with C from the inception of the databases to January 10, 2021. We performed frequentist NMA and indirect comparison to compare study outcomes from the included RCTs. The risk of bias of each study was assessed using the Cochrane risk of bias tool. Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). Results: A total of 31 RCTs with 1985 participants comparing 10 OCPM, namely, Antike (ATK), Shenyi (SY), Huachansu (HCS), Boerning (BEN), Xiaoaiping (XAP), Jinlong (JL), Compound matrine (CC), Pingxiao (PX), Xihuang pill (XHW), Kangaiping (KAP) were identified. The methodological quality of included RCTs was not very high. The results of the NMA showed that the comparisons were all indirect. Among diverse OCPM, ATK + C had the highest objective response rate (ORR) with a P-score of .63 with risk ratio (RR) of 1.37 (95% CI 1.12-1.66); with a RR of 1.96 (1.26-3.05), SY + C had the highest performance status with a P-score of .73; KAP + C had the lowest nausea and vomiting with a P-score of .91 and with a RR of 0.29 (0.10-0.79); and JL + C had lowest leukopenia with a P-score of .95 with a RR of 0.47 (0.31-0.72). The results of pairwise comparison suggested no difference in outcomes among 10 kinds of OCPM + C. The comparison-adjusted funnel plots suggested that there might not be small-study effects for outcomes. According to the CINeMa approach, the confidence rating of this NMA ranged from “very low” to “low” for various comparisons. Conclusion: Based on the NMA, ATK + C, SY + C, KAP + C and JL + C were associated with more preferable and options for CRC patients when referring to ORR, performance status, nausea and vomiting, and leukopenia, respectively. However, owing to the limitations of this research, the above conclusions require further verification by more high-quality RCTs. PROSPERO registration: CRD42020160658.