Anti-proliferative and Apoptotic Activities of Kasturi Tobacco (Nicotiana tabacum L.) Leaf Resinoid on Cervical Cancer Cell
Abstract
BACKGROUND: Cervical cancer has a high rate of morbidity and mortality in women with cancer. Recent studies have found that tobacco (Nicotiana tabacum L.) is a potential source of anti-cancer agents. Hence, this study was conducted to determine the potential of Kasturi tobacco leaf resinoids as apoptotic agents against cervical cell malignancies, since it has not been fully elucidated before.
METHODS: The phytochemical diversity of Kasturi tobacco resinoids was generated by gas chromatography-mass spectrometry (GC-MS) analysis followed by spectral similarity to National Institute of Standards and Technology (NIST) database. Cytotoxicity and proliferative activity of HeLa cells treated with Kasturi tobacco resinoids at various concentrations were evaluated by MTT assay. The expression of Caspase-3, cyclooxygenase-2 (COX-2) and heat shock protein 90 (HSP-90) in HeLa cells was analyzed by immunocytochemistry. Next, the migration ability of HeLa cells was observed by the scratch method.
RESULTS: Kasturi tobacco resin contains 4,8,13-cyclotetradecatriene-1,3-diol, 1,5,9-trim with α-2,7,11-cembratriene-4,6-diol (α-CBD) structure in the form of a diterpenoid compound with the chemical formula C20H34O2 and a molecular weight of 306 Da. Kasturi tobacco resinoid with IC50 value of 2500 μg/mL inhibited proliferative activity during 72 hours. At a concentration of 1¼ IC50 and incubation for 48 hours, Caspase-3 expression increased by 74.1%, while COX-2 and HSP-90 expression decreased by 28.3% and 26.1%, respectively. HeLa cell migration was inhibited by Kasturi tobacco resinoid at 24 hours incubation.
CONCLUSION: Kasturi tobacco resinoids with a concentration of 1¼ IC50 have potential as cervical anti-cancer agents by increasing Caspase-3 expression and decreasing COX-2 and HSP-90 expression within 48 hours.
KEYWORDS: Kasturi tobacco resinoids, cervical cancer, anti-cancer agent, proliferative activity
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Nedeltcheva-Antonova D, Ivanova D, Antonov L, Abe I. Insight into the aroma profile of Bulgarian tobacco absolute oil. Ind Crops Prod. 2016; 94: 226-32, CrossRef.
Popova V, Tumbarski Y, Ivanova T, Hadjikinova R, Stoyanova A. Tobacco resinoid (Nicotiana tabacum L.) as an active ingredient of cosmetic gels. J App Pharm Sci. 2019; 9(9): 111-8, CrossRef.
Banožić M, Banjari I, Jakovljević M, Šubarić D, Tomas S, Babić J, et al. Optimization of ultrasound-assisted extraction of some bioactive compounds from tobacco waste. Molecules. 2019; 24(8): 1611, CrossRef.
Rodgman A, Perfetti TA. The Chemical Components of Tobacco and Tobacco Smoke. 2nd ed. Boca Raton: CRC Press; 2013.
Bakht J, Azra, Shafi M. Antimicrobial activity of Nicotiana tabacum using different solvents extracts. Pak J Bot. 2012; 44(1): 459-63, article.
Yuan XL, Mao XX, Du YM, Yan PZ, Hou XD, Zhang ZF. Anti-tumor activity of cembranoid-type diterpenes isolated from Nicotiana tabacum L. biomolecules. 2019; 9(2): 45, CrossRef.
Kusumawardani B, Febi QN, Rosidah M, Azis DA, Puspitasari E, Nugraha AS. Cytotoxic potential of flavonoid from Nicotiana tabacum leaves on MCF-7 human breast cancer cells. Indones J Cancer Chemoprevent. 2020; 11(2): 97-102, CrossRef.
El Sayed KA, Sylvester PW. Biocatalytic and semisynthetic studies of the anticancer tobacco cembranoids. Expert Opin Investig Drugs. 2007; 16(6): 877-87, CrossRef.
Latief M, Rini IA, Pradini GW, Winarno GNA, Sahiratmadja E, Susanto H. Phylogenetic analysis of human papillomavirus 16 and 52 L1 gene from gervical cancer in Bandung, Indonesia. Indones Biomed J. 2018; 10(1): 40-5, CrossRef.
Gupta SM, Mania-Pramanik J. Molecular mechanisms in progression of HPV-associated cervical carcinogenesis J Biomed. 2019; 26(1): 28, CrossRef.
Lin CC, Yu CS, Yang JS, Lu CC, Chiang JH, Lin JP, et al. Chrysin, a natural and biologically active flavonoid, influences a murine leukemia model in vivo through enhancing populations of T-and B-cells, and promoting macrophage phagocytosis and NK cell cytotoxicity. In Vivo. 2012; 26(4): 665-70, PMID.
Tania L, Nugraha AS, Handoyo T, Kusumawardani B. Chemical composition of Kasturi tobacco resinoid determined by gas chromatography-mass spectrometry. Malays J Anal Sci. 2021; 25(4): 661-8, article.
Novilla A, Mustofa, Astuti I, Jumina, Suwito H. Cytotoxic activity of methoxy-4’amino chalcone derivates against leukimia cell lines. Mol Cell Biomed Sci. 2019; 3(1): 34-41, CrossRef.
Zhou Y, Yang Y, Li XL, Chen ZY, Liu QB, Zhu XL, et al. Determination of cembrenediols in tobacco by gas chromatography-mass spectrometry-selected ion monitoring with precolumn derivatization. Acta Chromatogr. 2016; 28(4): 513-24, CrossRef.
Al-Lihaibi SS, Alarif WM, Abdel-Lateff A, Ayyad SN, Abdel-Naim AB, El-Senduny F, et al. Three new cembranoid-type diterpenes from red sea coral Sarchophyton glaucum: isolation and antiproliferative activity againts HepG2 cells. Eur J Med Chem. 2014; 81: 314-22, CrossRef.
Yan N, Du Y, Liu X, Zhang H, Liu Y, Zhang P, et al. Chemical structures, biosynthesis, bioactivities, biocatalysis and semisynthesis of tobacco cembranoids: an overview. Ind Crops Prod. 2016; 83: 66-80, CrossRef.
Hassan HM, Sallam AA, Mohammed RAA, Hifnawy MS, Youssef DTA, El Sayed KA. Semisynthetic analogues of the marine cembranoid sarcophine as prostate and breast cancer migration inhibitors. Bioorg. 2011; 19(16): 4928-34, CrossRef.
Rahman MN, Novalentina M, Wijaya CR. Survivin clinical features in cervical cancer. Mol Cell Biomed Sci. 2017: 1(1): 6-16, CrossRef.
Ali MR, Yong MJ, Gyawali R, Mosaddik A, Ryu YC, Cho SK. Mango (Mangifera indica L.) peel extracts inhibit proliferation of HeLa human cervical carcinoma cell via induction of apoptosis. J Korean Soc Appl Biol Chem. 2012; 55(3): 397-405, CrossRef.
Günther A, Luczak V, Abel T, Baumann A. Caspase-3 and GFAP as early markers for apoptosis and arogliosis in shRNA-induced hippocampal cytotoxicity. J Exp Biol. 2017; 220(8): 1400-4, CrossRef.
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2012; 19: 107-20, CrossRef.
Pfeffer CM, Singh ATK. Apoptosis: a target for anticancer therapy. Int J Mol Sci. 2018; 19(2): 448-58, CrossRef.
Tsai TC, Lai KH, Wu JH, Sheu JH. 7-Acetylsinumaximol B induces apoptosis and autophagy in human gastric carcinoma cells through mitochondria dysfunction and activation of the PERK/elF2α/ATF4/CHOP signaling pathway. J Mar Drugs. 2018; 16(104): 2-13, CrossRef.
Fadholly A, Ansori ANM, Proboningrat A, Nugraha AP, Iskandar RPD, Rantam FA, et al. Apoptosis of HeLa cells via caspase-3 expression induced by chitosan-based nanoparticles of Annona squamosa leaf extract: in vitro study. Indian J Pharm Educ Res. 2020; 54(2): 416-21, CrossRef.
Yunguang LI, Demin PU, Yanli LI. The expression of cyclooxygenase-2 in cervical cancers and Hela cells was regulated by estrogen/progestogen. J Huazhong Univ Sci Technol Med Sci. 2007; 27(4): 457-60, CrossRef.
Deshpande R, Mansaraa P, Kaul-Ghanekar R. Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of P53 and Rb expression in human cervical cancer cell lines. Tumor Biol. 2016; 37(3): 3295-305, CrossRef.
Liu Q, Yuan W, Tong D, Liu G, Lan W, Zhang D, et al. Metformin represses bladder cancer progression by inhibiting stem cell repopulation Via COX2/PGE2/STAT3 axis. Oncotarget. 2016; 7(19): 28235-46, CrossRef.
Pan J, Yang Q, Shao J, Zhang L, Ma J, Wang Y, et al. Cyclooxygenase-2 induced beta1-integrin expression in NSCLC and promoted cell invasion via the EP1/MAPK/E2F-1/FoxC2 signal pathway. Sci Rep. 2016; 6: 33823, CrossRef.
Solárová Z, Mojžiš J, Solár P. Hsp90 Inhibitor as a sensitizer of cancer cells to different therapies (Review). Int J Oncol. 2015; 46(3): 907-26, CrossRef.
Hochberg GKA, Shepherd DA, Marklund EG, Santhanagoplan I, Degiacomi MT, Laganowsky A, et al. Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions. Science. 2018; 359(6378): 930-5, CrossRef.
Nurhayati, B, Rahayu IG, Rinaldi SF, Zaini WS, Afifah E, Arumwardana S, et al. The antioxidant and cytotoxic effects of Cosmos caudatus ethanolic extract on cervical cancer. Indones Biomed J. 2018; 10(3): 243-49, CrossRef.
Schopf FH, Biebl MM, Buchner J. The HSP90 chaperone machinery. Nat Rev Mol Cell Biol. 2017; 18(6): 345-60, CrossRef.
Schwock JN, Pham A, Cao MP, Hedley DW. Efficacy of Hsp90 inhibition for induction of apoptosis and inhibition of growth in cervical carcinoma cells in vitro and in vivo. Cancer Chemother. 2008; 61(4): 669-81, CrossRef.
Liao CL, Chu YL, Lin HY, Chen CY, Hsu MJ, Liu KC, et al. Bisdemethoxycurcumin suppresses migration and invasion of human cervical cancer HeLa cells via inhibition of NF-ĸB, MMP-2 and -9 pathways. Anticancer Res. 2018; 38(7): 3989-97, CrossRef.
DOI: https://doi.org/10.18585/inabj.v14i4.2027
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