자궁경부암에 대한 천남성의 세포사멸 유도를 통한 항암 효과
The Anticancer Effect of Arisaematis Rhizoma through Induction of HeLa Cell Apoptosis
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Objectives: This study was designed to examine the anticancer effects and principles of Arisaematis Rhizoma (AR) in a Human-derived cervical carcinoma cells (HeLa cells). Methods: To investigate the anticancer effects of AR, HeLa cells was tested with WST-1 to measure the viability of cells. The anti-cancer effects were determined by observing mitochondrial morphological change using Mito-TrackerTM stain and immuncytochemistry assay with Ki67 and Hoechst-33342 stain. Protein levels of apoptosis signals such as p38 and ERK were evaluated by western blot. Tomoholographic microscopy was used to evaluate lipid accumulation of HeLa cells. Results: AR significantly decreased cell viability of HeLa cells in a concentration- dependent manner. Mitochondrial length and the expression of Ki67, a marker for cell proliferation were significantly reduced while nuclear condensation significantly increased in HeLa cells treated with AR. The expression of p38 protein, a computational factor related to cell death, significantly increased. In addition, lipid accumulation significantly increased in HeLa cells treated with AR. Conclusions: AR increased the cytotoxicity of HeLa cells through cell death induced by mitochondrial fission, inhibition of cell proliferation, nuclear condensation and lipid accumulation. The expression of p38, which induces cell death, was upregulated. These results suggest that AR treatment may potentially have anticancer effects by inducing cell death in cervical cancer cells.
Abstract
Objectives: This study was designed to examine the anticancer effects and principles of Arisaematis Rhizoma (AR) in a Human-derived cervical carcinoma cells (HeLa cells). Methods: To investigate the anticancer effects of AR, HeLa cells was tested with WST-1 to measure the viability of cells. The anti-cancer effects were determined by observing mitochondrial morphological change using Mito-TrackerTM stain and immuncytochemistry assay with Ki67 and Hoechst-33342 stain. Protein levels of apoptosis signals such as p38 and ERK were evaluated by western blot. Tomoholographic microscopy was used to evaluate lipid accumulation of HeLa cells. Results: AR significantly decreased cell viability of HeLa cells in a concentration- dependent manner. Mitochondrial length and the expression of Ki67, a marker for cell proliferation were significantly reduced while nuclear condensation significantly increased in HeLa cells treated with AR. The expression of p38 protein, a computational factor related to cell death, significantly increased. In addition, lipid accumulation significantly increased in HeLa cells treated with AR. Conclusions: AR increased the cytotoxicity of HeLa cells through cell death induced by mitochondrial fission, inhibition of cell proliferation, nuclear condensation and lipid accumulation. The expression of p38, which induces cell death, was upregulated. These results suggest that AR treatment may potentially have anticancer effects by inducing cell death in cervical cancer cells.
참고문헌 (42)
- Bray F, "Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 70(4), pp.313~ (2020)
- National Cancer Center, "Korea Central Cancer Registry, National Cancer Center", Ministry of Health and Welfare, ~ (2020)
- Bhatla N, "Cancer of the cervix uteri : 2021 update", Int J Gynaecol Obstet, 155(Suppl 1), pp.28~44 (2021)
- Kim JH, "The burden of cervical cancer in Korea : a population-based Study", Int J Environ Res Public Health, 17(17), pp.6308~ (2020)
- Bansal N, "Primary therapy for early-stage cervical cancer : radical hysterectomy vs radiation", Am J Obstet Gynecol, 201(5), pp.485~ (2009)
- Weinmann S, "Pregnancy outcomes after treatment for cervical cancer precursor lesions : an observational study", PLoS One, 12(1), pp.e0165276~ (2001)
- Vistad I, "A critical review of patient-rated quality of life studies of long-term survivors of cervical cancer", Gynecol Oncol, 102(3), pp.563~572 (2006)
- Cosgrove CM, "Ovarian effects of radiation and cytotoxic chemotherapy damage", Best Pract Res Clin Obstet Gynaecol, 55, pp.37~48 (2019)
- Yoo JE, "A review on Korean traditional medicine research against cervical dysplasia-focused on studies of cervical cancer and cervical dysplasia", J Orient Gyn, 26(4), pp.191~203 (2013)
- CY Qi, "Botanical, traditional use, phytochemical, and toxicological of arisaematis rhizome", Evid-Vased Compl Alt Med, 30, pp.9055574~ (2021)
- Chen XY, "Proteomics study of total protein of pinellia pedatisecta schott effect on human ovarian cancer SKOV3 cells", Chin J Integr Trad Med, 31(12), pp.1651~1656 (2011)
- Chen G, "Characterization and antitumor activities of the watersoluble polysaccharide from rhizoma arisaematis", Carbohydr Polym, 90(1), pp.67~72 (2012)
- Bae WJ, "Inhibitory effects of arisaematis rhizoma on cell proliferation in HeLa cell", J Orient Gyn, 19(3), pp.25~40 (2006)
- SOG Gynecologic Oncology Committee, "Annual report of gynecologic cancer registry program in Korea for 2004(Jan. 1st, 2004-Dec. 31st, 2004)", Korean J Obstet Gynecol, 50, pp.28~78 (2007)
- Kim KT, "Prognosis of stage IIB cervical cancer among treatment regimens : radical hysterectomy vs. neoadjuvant chemotherapy followed by radical hysterectomy vs. concurrent chemoradiotherapy", Obstet Gynecol Sci, 55(12), pp.913~919 (2012)
- Green JA, "Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix : a systematic review and metaanalysis", Lancet, 358(9284), pp.781~786 (2001)
- Shin JN, "A literatural study on oriental medical therapy for uterine carcinoma", Department of East-West Medical Science, pp.2008
- Shin JS, "Bibliographical review on oriental medicine herbal treatment for uterine carcinoma", J Physiol &Pathol Korean Med, 22(3), pp.507~515 (2008)
- Choi YS, "Anti-tumor effect of amygdalin extracted from armeniacae amarum semen on human cervical cancer cell ME-180", J Korean Med Opthalmol Otolaryngol Dermatol, 32(3), pp.1~12 (2019)
- Lee JG, "Growth arrest and apoptosis of Human uterine cervical carcinoma cells induced by trichosanthes semen extract", J Physiol & Pathol Korean Med, 19(4), pp.965~972 (2005)
- Han KG, "A literature review of the origins and efficacy of chunnamseong", Kor J Herb, 8(1), pp.37~84 (1993)
- Zhang MC, "Study on effect of pinellia pedatisecta schott protein on proliferation of lung cancer cells", J Modern Med & Health, 32(24), pp.3760~3762 (2016)
- Li F, "Effect of water extract of rhizoma arisaema on the expression of PKMW and mTOR genes in gastric cancer rat cells", Modern Food Sci Tech, 35(12), pp.41~46 (2019)
- Li GL, "HPV E6 down-regulation and apoptosis induction of human cervical cancer cells by a novel lipid-soluble extract(PE)from pinellia pedatisecta schott in vitro", J Ethnopharmacol, 132(1), pp.56~64 (2010)
- Wong RS, "Apoptosis in cancer : from pathogenesis to treatment", J Exp Clin Cancer Res, 30(1), pp.87~ (2011)
- Jeong SY, "The role of mitochondria in apoptosis", BMB Rep, 41(1), pp.11~22 (2008)
- Kleele T, "Distinct fission signatures predict mitochondrial degradation or biogenesis", Nature, 593(7859), pp.435~439 (2021)
- Elmore S, "Apoptosis : a review of programmed cell death", Toxicol Pathol, 35(4), pp.495~516 (2007)
- Atale N, "Cell-death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques", J Microsc, 255(1), pp.7~19 (2014)
- Shi Q, "Ki-67 and P16 proteins in cervical cancer and precancerous lesions of young women and the diagnostic value for cervical cancer and precancerous lesions", Oncol Lett, 18(2), pp.1351~1355 (2019)
- R DP, "An immunohistochemical study on Ki-67 expression in squamous cell carcinomas of Cervix with clinicopathological correlation", Cureus, 15(1), pp.e34155~ (2023)
- Wagner EF, "Signal integration by JNK and p38 MAPK pathways in cancer development", Nat Rev Cancer, 9(8), pp.537~549 (2009)
- Guo YJ, "ERK", MAPK signalling pathway and tumorigenesis, 2020, pp.19(3), 1997~2007
- Sugiura R, "ERK : A double-edged sword in Cancer. ERKdependent apoptosis as a potential therapeutic strategy for cancer", Cells, 10(10), pp.2509~ (2021)
- Barbosa R, "The MEK", ERK network as a therapeutic target in human cancer, 2021, pp.19(3), 361~374
- Dolado I, "P38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis", Cancer Cell, 11(2), pp.191~205 (2007)
- Martínez-Limón A, "The p38pathway : from biology to cancer therapy", Int J Mol Sci, 21(6), pp.1913~ (2020)
- Olson JM, "P38 MAP kinase : a convergence point in cancer therapy", Trends Mol Med, 10(3), pp.125~129 (2004)
- Yan HF, "Ferroptosis : mechanisms and links with diseases", Signal Transduct Target Ther, 6(1), pp.49~ (2021)
- Bai YS, "Lipid storage and lipophagy regulates ferroptosis", Biochem Biophys Res Commun, 508(4), pp.997~1003 (2019)
- Blankenberg FG, "In vivo detection of apoptosis", J Nucl Med, 49(Suppl 2), pp.81S~95S (2008)
- Chang X, "Ferroptosis : mechanism and potential applications in cervical cancer", Front Mol Biosci, 10, pp.1164398~ (2023)