A novel herbal formula, SGE, induces endoplasmic reticulum stress-mediated cancer cell death and alleviates cachexia symptoms induced by colon-26 adenocarcinoma.

Aeyung Kim,Jin Yeul Ma,Minju Im

doi:10.18632/oncotarget.24616

Aeyung Kim, Jin Yeul Ma + Show 1 more

Open Access

https://doi.org/10.18632/oncotarget.24616

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Journal: Oncotarget	Publication Date: Mar 27, 2018
Citations: 8	License type: cc-by

Affiliation: Korea Institute of Oriental Medicine

Abstract

Cachexia in cancer patients, characterized by marked involuntary weight loss and impaired physical function, is associated with a poor prognosis in response to conventional treatment and with an increase in cancer-related mortality. Prevention of skeletal muscle loss under cancer-induced cachexia via inhibition of pro-cachectic factors, as well as a reduction in tumor mass, has been considered reasonable pharmacological and nutritional interventions to treat cancer patients. In this study, we constructed a novel herbal formula, SGE, which contains Ginseng Radix alba, Atractylodis Rhizoma alba, and Hoelen, examined its anti-cancer and anti-cachexia efficacies. In in vitro experiments, SGE induced death of CT-26 murine colon carcinoma cells via endoplasmic reticulum stress, and suppressed the production of inflammatory cytokines in Raw 264.7 murine macrophage-like cells. In addition, SGE treatment attenuated CT-26-induced C2C12 skeletal muscle cell atrophy as well as CT-26-induced reduction in lipid accumulation in 3T3-L1 adipocyte. In CT-26 tumor-bearing mice, daily oral administration of 10 and 50 mg/kg SGE remarkably attenuated the cachexia-related symptoms, including body weight and muscle loss, compared with saline treatment, while food intake was not affected. These data collectively suggest that SGE is beneficial as an anti-cancer adjuvant to treat cancer patients with severe weight loss.

Highlights

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancerrelated deaths in adults in the U.S [1, 2]
Because SGE is an herbal mixture consisting of three herbs Ginseng Radix alba, Atractylodis Rhizoma alba, and Hoelen, we examined the effects of ethanol extracts of each herb on cell viability
The word “Cachexia” comes from the Greek words kakos, meaning bad, and hexia, meaning condition, and describes a multifactorial wasting syndrome characterized by excessive weight loss and depletion of fat and skeletal muscle

Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancerrelated deaths in adults in the U.S [1, 2]. CRC patients demonstrate various symptoms, such as rectal bleeding, persistent abdominal discomfort, changes in bowel habits including constipation or diarrhea, weakness or fatigue, and decreased appetite [4]. More than 50% of CRC patients experience unintentional weight loss with severe muscle wasting, and this condition, which is distinct from starvation and age-related muscle loss, cannot be prevented or recovered by conventional nutritional support [5, 6]. In cancer patients, wasting syndrome, including anorexia, metabolic and endocrine alterations, fatigue, and loss of lean body mass, is known as cancer cachexia, and this condition diminishes the efficacy of conventional chemotherapy and radiotherapy, reduces quality of life, and worsens the prognosis of cancer patients. To overcome colon cancer, it is necessary to suppress cancer cells directly and control cancer-induced cachectic symptoms, for preservation of lean body mass

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