The Prevention And Treatment Efficacy Of Compound Coix Seed Oil (C-ASO) On Skin Carcinogenesisl And Its Mechanisms

BackgroundCancer poses a serious threat to human life around the world,and it is undoubtedly one of the leading causes of death in both developed and relatively advanced medical countries.Skin cancer is a relatively common malignant tumor that occurs in human skin and is generally divided into malignant melanoma,basal cell carcinoma,and squamous cell carcinoma.Skin cancer treatment options include surgery,radiotherapy,Chinese medicine,etc.Prevention is the main factor in reducing the screening,treatment and mortality burden of skin cancer.Therefore,it is very important to pay attention to the prevention of skin cancer.There have been many reports in the literature that obesity is one of the risk factors associated with cancer-related mortality,but it is still controversial in the development of skin cancer.Coix Seed oil is extracted from the Chinese medicine Coix Seed.KLTI,a proprietary Chinese medicine used for various cancer treatments,is mainly composed of Coix Seed oil,which also has a role in reducing abdominal fat.The main active ingredient of cinnamon,cinnamaldehyde,which widely used in cooking,has anti-obesity and anti-tumor effects.and ginger-containing main substance,6-gingerol,also has anti-adipogenesis and anti-tumor effects.PurposeIn this study,a composite kernel oil(C-ASO)containing 0.5% cinnamaldehyde and 1% 6-gingerol was prepared,and oral C-ASO was evaluated against 9,10-dimethylbenzopyrene(DMBA)/12-Otetradecyl polyoxyethylene-13-acetate(TPA)-induced skin cancer prevention and treatment.MethodsA mouse model of ICR was used to establish a DMBA/TPA-induced skin cancer model,a standard rodent diet(SRC).Cinnamaldehyde,6-gingerol,Coix-caulis oil,and composite carotenoid oil(complex)which contained cinnamaldehyde and 6-gingerol were administered by gavage daily.The body weight of mice,the incidence and diversity of skin cancer,the number of tumor nodules,and the diameter of tumors were recorded to observe changes in physiological signs of mice.the pathologic changes of the skin of mice were assessed by HE staining.The changes of EMT process in mice with skin cancer modelinduced by DMBA/TPA were detected by immunohistochemistry.To explore why C-ASO synergistically reduced susceptibility to skin carcinogenesis,we examined DMBA/TPA-associated changes in serm cholesterol,cell membrane lipid rafts by plasma membrane cholesterol and GM1 staining,and cellular signaling such as PI3 K,Akt,NF-?B and cyclin D1 by western blot analyses at 21 weeks.To verify the synergistical effect of C-ASO on cancer prevention,we also examined DMBA/TPA-associated changes in skin epithelial proliferation and EMT by immunohistochemistry at 21 weeks.ResultsThe results showed that,Under these experimental conditions,oral treatment of ASO,cinnamaldehyde and gingerol alone or combined had no effect on body weight,whereas C-ASO led to lean body phenotypes(<fifteen percent of normal body weight).In contrast to untreated carcinogenic mice,skin tumor incidence and multiplicity were decreased to some extent in single ASO-treated,cinnamaldehydetreated and gingerol-treated mice.However,C-ASO almost completely reduced susceptibility to skin carcinogenesis.;compared with the model group,cutaneous tumors in mice treated with cinnamaldehyde,gingerol,or leucin oil,respectively,The number and the size of tumors were reduced to some extent.However,they decreased more significantly in the C-ASO mice.Consistent with above results,serum levels of IL-6,hs-CRP and TNF-? were decreased to some extent in single ASO-treated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by C-ASO compared to untreated carcinogenic mice.Similarly,serum levels of 8-OHdG and ROS were only decreased to some extent in single ASO-treated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by C-ASO;Consistently,the skin cell lipid rafts were decreased to some extent in single ASOtreated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by CASO compared to untreated carcinogenic mice.Similarly,the skin protein expression of PI3 K,Akt,NF-?B and cyclin D1 was only decreased to some extent in single ASO-treated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by C-ASO.Carcinogenesis is the final results of epithelial proliferation and EMT.Consistent with above results,PCNA,a skin epidermal proliferation marker,were decreased to some extent in single ASO-treated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by C-ASO compared to untreated carcinogenic mice.Similarly,lung EMT indicated by E-cadherin and N-cadherin were only decreased to some extent in single ASO-treated,cinnamaldehyde-treated and gingerol-treated mice but were very significantly suppressed by CASO.conclusion,C-ASO can reduce fat and prevent DMBA/TPA-induced mouse skin carcinogenesis,and its mechanism of action is accomplished by lipid raft ablation.