Similar articles

Abstract: ObjectivePrimary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-‍α‍-tocopheryl succinic acid (VES),β‍-carotene (β‍-Ca), and L-lysine (Lys).
MethodsThe effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo.
ResultsMVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function.
ConclusionsThis study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.

L-Se-甲基硒代半胱氨酸、D-α-生育酚琥珀酸酯、β-胡萝卜素和L-赖氨酸联合作为辅助治疗手段可预防肿瘤转移

[1]Abu SamaanTM, SamecM, LiskovaA, et al., 2019. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules, 9(12):789.

[2]AveryJC, HoffmannPR, 2018. Selenium, selenoproteins, and immunity. Nutrients, 10(9):1203.

[3]BarrettM, Uí DhuibhirP, NjorogeC, et al., 2020. Diet and nutrition information on nine national cancer organisation websites: a critical review. Eur J Cancer Care (Engl), 29(5):e13280.

[4]CheungEC, DenicolaGM, NixonC, et al., 2020. Dynamic ROS control by TIGAR regulates the initiation and progression of pancreatic cancer. Cancer Cell, 37(2):168-182.e4.

[5]CrowderSW, HortonLW, LeeSH, et al., 2013. Passage-dependent cancerous transformation of human mesenchymal stem cells under carcinogenic hypoxia. FASEB J, 27(7):2788-2798.

[6]DikicI, ElazarZ, 2018. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol, 19(6):349-364.

[7]FangYZ, YangS, WuGY, 2002. Free radicals, antioxidants, and nutrition. Nutrition, 18(10):872-879.

[8]GanashMA, 2021. Anticancer potential of ascorbic acid and inorganic selenium on human breast cancer cell line MCF-7 and colon carcinoma HCT-116. J Cancer Res Ther, 17(1):122-129.

[9]GuoYY, XiaoYY, GuoHC, et al., 2021. The anti-dysenteric drug fraxetin enhances anti-tumor efficacy of gemcitabine and suppresses pancreatic cancer development by antagonizing STAT3 activation. Aging (Albany NY), 13(14):18545-18563.

[10]HébertJR, HurleyTG, SteckSE, et al., 2014. Considering the value of dietary assessment data in informing nutrition-related health policy. Adv Nutr, 5(4):447-455.

[11]HuangXL, NeckenigM, SunJT, et al., 2021. Vitamin E succinate exerts anti-tumour effects on human cervical cancer cells via the CD47-SIRPα pathway both in vivo and in vitro. J Cancer, 12(13):3877-3886.

[12]Ibrahim-HashimA, WojtkowiakJW, de Lourdes Coelho RibeiroM, et al., 2011. Free base lysine increases survival and reduces metastasis in prostate cancer model. J Cancer Sci Ther, Suppl 1(4):JCST-S1-004.

[13]JiangQ, 2017. Natural forms of vitamin E as effective agents for cancer prevention and therapy. Adv Nutr, 8(6):850-867.

[14]JiangZW, ChiJH, LiH, et al., 2021. Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth. Eur J Pharmacol, 891:173673.

[15]KimYS, LeeHA, LimJY, et al., 2014. β-Carotene inhibits neuroblastoma cell invasion and metastasis in vitro and in vivo by decreasing level of hypoxia-inducible factor-1α. J Nutr Biochem, 25(6):655-664.

[16]KirchhainA, ZubrienėA, KairysV, et al., 2021. Biphenyl substituted lysine derivatives as recognition elements for the matrix metalloproteinases MMP-2 and MMP-9. Bioorg Chem, 115:105155.

[17]KontekR, JakubczakM, Matlawska-WasowskaK, 2014. The antioxidants, vitamin A and E but not vitamin C and melatonin enhance the proapoptotic effects of irinotecan in cancer cells in vitro. Toxicol in Vitro, 28(2):282-291.

[18]LiCH, LiYF, YaoTT, et al., 2020. Wireless electrochemotherapy by selenium-doped piezoelectric biomaterials to enhance cancer cell apoptosis. ACS Appl Mater Interfaces, 12(31):34505-34513.

[19]LiuXY, PeiCY, YanS, et al., 2015. NADPH oxidase 1-dependent ROS is crucial for TLR4 signaling to promote tumor metastasis of non-small cell lung cancer. Tumor Biol, 36(3):1493-1502.

[20]MaL, LiuL, MaYC, et al., 2017. The role of E-cadherin/β-catenin in hydroxysafflor yellow a inhibiting adhesion, invasion, migration and lung metastasis of hepatoma cells. Biol Pharm Bull, 40(10):1706-1715.

[21]MarianM, AugustDA, 2014. Prevalence of malnutrition and current use of nutrition support in cancer patient study. J Parenter Enteral Nutr, 38(2):163-165.

[22]Martínez-ReyesI, ChandelNS, 2021. Cancer metabolism: looking forward. Nat Rev Cancer, 21(10):669-680.

[23]ØrskovH, FlyvbjergA, 2000. Selenium and human health. Lancet, 356(9233):942-943.

[24]PrasadS, GuptaSC, TyagiAK, 2017. Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Cancer Lett, 387:95-105.

[25]RoomiMW, IvanovV, KalinovskyT, et al., 2005. In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7. Med Oncol, 22(2):129-138.

[26]SatomiY, NishinoH, 2013. Inhibition of the enzyme activity of cytochrome P450 1A1, 1A2 and 3A4 by fucoxanthin, a marine carotenoid. Oncol Lett, 6(3):860-864.

[27]ShimojoY, AkimotoM, HisanagaT, et al., 2013. Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells. Clin Exp Metastasis, 30(2):143-154.

[28]SiegelRL, MillerKD, FuchsHE, et al., 2022. Cancer statistics, 2022. CA Cancer J Clin, 72(1):7-33.

[29]SuX, ShenZ, YangQ, et al., 2019. Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics, 9(15):4461-4473.

[30]WangYW, QiH, LiuY, et al., 2021. The double-edged roles of ROS in cancer prevention and therapy. Theranostics, 11(10):4839-4857.

[31]ZhangT, ZhuXY, WuHC, et al., 2019. Targeting the ROS/PI3K/AKT/HIF-1α/HK2 axis of breast cancer cells: combined administration of Polydatin and 2-Deoxy-d-glucose. J Cell Mol Med, 23(5):3711-3723.

[32]ZhouMG, WangHD, ZengXY, et al., 2019. Mortality, morbidity, and risk factors in China and its provinces, 1990‒2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 394(10204):1145-1158.

[33]ZhouX, JiWJ, ZhuY, et al., 2007. Enhancement of endogenous defenses against ROS by supra-nutritional level of selenium is more safe and effective than antioxidant supplementation in reducing hypertensive target organ damage. Med Hypotheses, 68(5):952-956.