Sanjie Yiliu Formula Inhibits Colorectal Cancer Growth by Suppression of Proliferation and Induction of Apoptosis

Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. As current therapies toward CRC, including chemotherapy and radiotherapy, pose limitations, such as multidrug resistance (MDR) as well as the intrinsic and potential cytotoxic effects, necessitating to find more effective treatment options with fewer side effects, traditional Chinese medicine (TCM) has an advantage in complementary therapies. In the present study, 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assays), trypan blue staining, colony formation, 4,6-diamidino-2phenylindole dihydrochloride (DAPI) staining, cell cycle determination, and Annexin V-FITC/PI staining were used to examine the efficacy of Sanjie Yiliu Formula (SJYLF) against CRC proliferation and to investigate its underlying molecular mechanisms through protein expression of various proapoptotic factors by quantitative polymerase chain reaction (q-PCR) and Western blotting. This four-herb-TCM SJYLF can be suggested as one of the decoctions clinically effective in late-stage cancer treatment. Our results suggest that SJYLF robustly decreased the viability of only CRC cell lines (HCT-8, SW-480, HT-29, and DLD-1) and not the normal human kidney cells (HK-2). Moreover, SJYLF significantly suppressed proliferation and induced apoptosis in HCT-8 and downregulated cyclin D1, CDK4, and BCL-2, while Bax expression was upregulated at both mRNA and protein expression levels.

Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer

“…In the treatment of PLGC, TCM acts mainly by regulating cell proliferation and apoptosis ( Xu et al, 2022 ). The role of TCM in the treatment of CRC has been reported, and data support the benefits of TCM herbals as a long-term therapeutic strategy for patients with stage II and III CRC ( Li-Weber, 2013 ; Li et al, 2021b ; Tang et al, 2021 ). TCM can interact with gut microbiota, which has a considerable influence on the therapeutic effects ( Feng et al, 2021 ).…”

In Vivo and In Silico Assessment of the Cardioprotective Effect of Thymus linearis Extract against Ischemic Myocardial Injury

“…. Multiple synthetic drugs exhibit substantial protection against oxidative stress/damage, but they have many adverse effects like cardiovascular diseases, hepatotoxicity, nephrotoxicity, and gastrointestinal tract problems. , Alternative options for safer use are the consumption of traditional medicine, natural antioxidants from food supplements, and herbal and polyherbal formulations . Doxorubicin has been used extensively and effectively as a broad-spectrum anticancer drug, although its medical use has been limited due to its severe dose-dependent cardiotoxicity in humans .…”

“… 15 , 16 Alternative options for safer use are the consumption of traditional medicine, natural antioxidants from food supplements, and herbal and polyherbal formulations. 17 Doxorubicin has been used extensively and effectively as a broad-spectrum anticancer drug, although its medical use has been limited due to its severe dose-dependent cardiotoxicity in humans. 18 Experimental and clinical analysis suggested that increased oxidative stress and/or ROS play a crucial role in consequent cardiomyopathy and cardiac failure related to the doxorubicin treatment model.…”

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

“…The experiment selected four CRC cells and found that the Sanjie Yiliu formula (SJYLF) significantly inhibited the activity of HCT-8, SW480, HT29, and DLD-1 CRC cells. SJYLF components, consisting of Fabanxia, Glabrous Sarcandra herb, Thunberg Fritillary bulb, and ground beetle species, initiated apoptosis through downregulating Bcl-2, cylin D1, and CDK4 protein, as well as increasing Bax expression ( Tang et al, 2021 ). Besides, Sijunzi decoction (SJZD) consistsing of Panax ginseng C.A.Mey., Atractylodes macrocephala Koidz., Poria cocos Wolf., and Glycyrrhiza uralensis Fisch., proportioned at a ratio of 2:2:2:1 and clinically used in treating CRC.…”