Lignans: a versatile source of anticancer drugs
Beni-Suef University Journal of Basic and Applied Sciences volume 11, Article number: 76 (2022)
Cancer is considered as the second deadliest disease globally. Plants have continuously offered unique secondary metabolites with remarkable biological applications. Lignans have gained great importance due to their biological activity. Previous studies revealed that the most remarkable bioactivity of lignan class of molecules is anticancer. They are derived from the oxidative dimerization of two phenylpropanoid units. This review covers the isolated anticancer lignans and their mechanistic aspects.
A bibliographic investigation was performed by analyzing the information available on anticancer lignans in the internationally accepted scientific databases including Web of Science, SciFinder, PubMed, Scopus, and Google Scholar. In this review we have tried to sum up the isolated anticancerous lignan, its source, active plant part, extract and various cell lines used to establish different studies. Here we have included a total number of 113 natural lignans. Many studies that mainly performed in human cell lines have reported. Very few plants have been evaluated for their in vivo anticancer activity.
It can be concluded that in near future the lignans may be an effective pharmacon for the treatment of cancer. Fruitful areas of future research may be in modifying natural lignans or synthesizing new lignans with structural diversity and potent pharmacological activities. Extensive studies are needed to be done highlighting the mechanism of anticancer action of explored and unexplored plants. The data will definitely attract many researchers to start further experimentation that might lead to the drugs for the cancer treatment.
There is a great burden of disease internationally and cancer is in the top priority due to its high incidence rate that causes disability and premature mortality among human populations .
Cancer is not a single disease but it is a group of 100 different and distinguishing disorders that affect the entire physiological balances . It is an uncontrolled growth of cells that have damaged DNA expression . If the spread of these abnormal cells is not managed with certain means, it can lead to worse situations or may be death. These abnormal cells are termed as cancer cells, malignant cells, or tumor cells. Many cancers that comprises of abnormal cells are further recognized by the name of the organ that the abnormal cells originated from (for example, breast cancer, lung cancer, prostate cancer, and colorectal cancer). There are various kinds of cancers depends upon the type of genes associated with specific cancer like sarcomas, carcinomas, leukemia, and lymphomas. Carcinogenesis is a multi-leveled process consists of three noticeable stages, i.e., initiation, promotion, and progression . It is the prime result of disturbances that occurred in two types of genes, tumor suppressor genes (TSG) and oncogenes.
Deaths from cancer are rising continuously worldwide with an estimated 11.5 million deaths in 2030 . The International Agency for Research on Cancer (IARC) estimated a shocking number of 19.3 million new cases including every possible distribution criteria (Fig. 1a, b) and approx 10 million of reported death worldwide .
Globally, non-communicable diseases (NCDs) accounted for 71% of total deaths. In India, NCDs were estimated to account for 63% of all deaths, and cancer was one of the leading causes (9%). The projected number of patients with cancer in India is 1,392,179 for the year 2020, and the common five leading origins are breast, lung, mouth, cervix uteri, and tongue . Persons with any type of existing cancer are prone to get affected with coronavirus (SARS-CoV-2), and it is a deadly combination for individuals . Studies revealed that prostate and breast cancer constitutes major types of cancer found, respectively, in men and women . In children the blood cancer and the cancers related to the brain and lymph nodes are more frequent than other types of cancer [10, 11]. There are certain risk factors that increase the development of cancer in any person such as ageing, tobacco, ionizing radiation, some chemical compounds, some viruses and bacteria, alcohol consumption, family history of cancer, certain hormones, and overweight .
The treatment options of cancer involve surgery of tumor, radiotherapy and chemotherapy depends upon the stage and location of tumor . But these treatments are very costly and require highly specialized health professionals . Additionally, these chemotherapeutic agents are not free from side effects like myelosuppression, mucositis, alopecia, cardiotoxicity, neurotoxicity, immunosuppression, etc. An ideal anticancer drug would specifically be cytotoxic toward the cancer cells only and research findings suggests that phytochemicals and their derivatives are emerging alternatives for better and less toxic chemotherapeutic agents .
Various active compounds such as podophyllotoxin, vincristine, vinblastine, taxol, etc., have been isolated from plants, and these molecules acted as lead metabolites to modify and yield analogues better than the parent compound for activity with low toxicity and improved bioavailability [15,16,17].
There are diverse classes of secondary metabolites which are biosynthesized by plants and, among them, lignans are identified as the major group of natural products with a broad range of important bioactivities.
2 Main text
Lignans are the class of plant secondary metabolites derived from the phenylpropanoid pathway and was first introduced by Haworth . They play an important role in plant protection and are also proved to be fruitful in human nutrition and medicine . The chief sources of dietary lignans are various vegetables and fruits, legumes, whole grain cereals, and oilseeds [20, 21]. Sesame and flax seeds are the edible plant components which are the most concentrated sources of lignans .
2.1 Chemistry of lignans
It is well-established that the supergroup of natural phenolics is biosynthesized through the shikimic acid pathway. The biodiversity of this lignan class of molecules is found in various parts of more than 60 families of plants and they are potential bioactive principles toward cancerous cells. Beside their cytotoxic property they are also useful to treat diabetes, oxidation of living cells as antioxidants, cardiovascular diseases, microbial infections, and other major or minor inflammatory responses [23, 24]. As per the earlier findings, the basic structure of lignan contains the nine carbon (in a C6-C3 fusion) phenylpropane unit (Fig. 2a) from cinnamyl structures  which was redefined by Haworth  as dimer of C6-C3 unit via β-β′ bonding (Fig. 2b). Besides this basic hydrocarbon skeleton they possess numerous additional side groups either in the form of aliphatic or aromatic origin and they are classified accordingly. There are eight subtypes of major lignans (Fig. 3) such as dibenzylbutane (e.g., Enterodiol), dibenzylbutyrolactone (e.g., Enterolactone), dibenzylbutyrolactol (e.g., Gnetucleistol F), dibenzocyclooctadiene (e.g., Gomisins), aryltetralin (e.g., Podophyllotoxins), arylnaphthalene (e.g., Justcidins), furan (e.g., Belischmins), and furofuran (e.g., Epimagnolin) derivatives. Except these eight subtypes, they are also diversified based on the presence or absence of oxygen [26, 27]. Hybrid lignans are molecules which have other secondary metabolites like flavonoids (flavolignans), coumarins (coumarinolignans), xanthones (xantholignans), stilbenes (stilbenolignans), etc., and possess lignan like biological and chemical properties.
The discovery of Podophyllotoxins as gold standard in leading lignans along with establishing its cytotoxic property and topoisomerase-II inhibitory potentials helped the research community to develop other clinically important drugs like etoposide, teniposide, clinical candidates like Etopophos, NK611, GL331, etc. . Ward reported a total number of 83 synthetic and transformational schemes including stereospecific and asymmetric consideration  to obtain them in laboratory.
There is persistent interest in the cancer-protective effects of lignans, which have been shown to have an advantageous anti-tumor effect throughout the early phases of carcinogenesis. The present review, summarizes the recent literature which deals with the lignans isolated from plants having anticancer potential with their reported mechanism of action which are listed in Table 1. Lignans has been considered as the promising anticancer agents.
3 Material and methods
The bibliography was crucially analyzed from worldwide established scientific databases like SCOPUS, PubMed, ScienceDirect, Springerlink, Web of Science, Wiley, SciFinder, and Google Scholar. The botanical names of these selected plant species were verified from the plant list. The inclusion criteria for the selection of data are lignans isolated from Medicinal plants with reported anticancer activity. Both the reviews and the research articles on medicinal plants are considered. The search terms were lignans, anticancer plants containing lignans, chemistry of lignans without narrowing or limiting search items.
Lignans are secondary metabolites are also phenolic in nature and have diversity in biological activities. Previous studies revealed that the most remarkable bioactivity of lignan class of molecules are antioxidant and anticancer. This review covers a considerable number of naturally obtained lignans that are reported to have anticancer potential. In this review we have tried to sum up the isolated anti-cancerous lignan, its source, active plant part, extract and various cell lines used to establish different studies. Here we have included a total 113 numbers of natural lignans. Many studies that mainly performed in human cell lines have reported inhibition of enzymes that retards tumor growth. Very few plants have been evaluated for their in vivo anticancer activity.
It can be concluded that in near future the lignans may be an effective pharmacon for the treatment of cancer. Fruitful areas of future research may be in modifying natural lignans or synthesizing new lignans with structural diversity and potent pharmacological activities. However, among the vast numbers of existing plants on this planet, only a few species have been studied so far for their anticancer principles. Extensive studies are needed to be done highlighting the mechanism of anticancer action of explored and unexplored plants.
Potent anticancer lignans reported in this review needed to be further explored in clinical trials on different models for their effectiveness, toxicological studies, and also targeting particular genotoxic profile against a wide range of cancer in both in vitro and in vivo. These compounds are obtained from plants in very minute quantities so this is one of the main challenges to be addressed in the future and their total synthesis in order to allow further bioactivity studies. The data will definitely attract many researchers to start further experimentation that might lead to the drugs for the cancer treatment and to manufacture new herbal drugs which have significant anticancer potential.
Availability of data and materials
Shih AH, Abdel-Wahab O, Patel JP, Levine RL (2012) The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer 12(9):599–612. https://doi.org/10.1038/nrc3343
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. https://doi.org/10.1016/s0092-8674(00)81683-9
Gilbert S (2011) From the Toxipedia website in original form. Last updated by Toxipedia in 2011. https://www.healthandenvironment.org/docs/ToxipediaCancerPageArchive.pdf
Kaur S, Pandit K, Chandel M, Kaur S (2020) Antiproliferative and apoptogenic effects of Cassia fistula L. n-hexane fraction against human cervical cancer (HeLa) cells. Environ Sci Pollut Res Int 27(25):32017–32033. https://doi.org/10.1007/s11356-020-08916-9
World health organization (2009) NMH Fact sheet January 2010. https://www.who.int/nmh/publications/fact_sheet_cancers_en.pdf
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660
Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, Nallasamy V, John A, Narasimhan S, Roselind FS (2020) Cancer statistics, 2020: report from National Cancer Registry Programme, India. JCO Glob Oncol 6:1063–1075. https://doi.org/10.1200/go.20.00122
Wang Q, Berger NA, Xu R (2021) Analyses of risk, racial disparity, and outcomes among US patients with cancer and COVID-19 infection. JAMA Oncol 7(2):220. https://doi.org/10.1001/jamaoncol.2020.6178
Siegel RL, Miller KD, Jemal A (2016) Cancer statistics 2016. CA Cancer J Clin 66:7–30
Schottenfeld D, Fraumeni JF (2006) Cancer epidemiology and prevention. Oxford University Press, England
Yoo KY, Shin HR (2003) Cancer epidemiology and prevention. Korean J Epidemiol 25:1–15
Cunha JP (2021) Medicine Net. Cancer risk factors and causes. Medically Reviewed on 5/17/2021. https://www.medicinenet.com/cancer_causes/article.htm
Singh S, Sharma B, Kanwar SS, Kumar A (2016) Lead phytochemicals for anticancer drug development. Front Plant Sci. https://doi.org/10.3389/fpls.2016.01667
Tariq A, Mussarat S, Adnan M (2015) Review on ethnomedicinal, phytochemical and pharmacological evidence of Himalayan anticancer plants. J Ethnopharmacol 164:96–119. https://doi.org/10.1016/j.jep.2015.02.003
Ambrosio SR, Tirapelli CR, da Costa FB, de Oliveira AM (2006) Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility. Life Sci 79(10):925–933. https://doi.org/10.1016/j.lfs.2006.05.015
Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O (2020) Phytochemicals in cancer treatment: from preclinical studies to clinical practice. Front Pharmacol 10:1614. https://doi.org/10.3389/fphar.2019.01614
Lichota A, Gwozdzinski K (2018) Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 19(11):3533. https://doi.org/10.3390/ijms19113533
Haworth RD (1942) The chemistry of the lignan group of natural products. J Chem Soc. https://doi.org/10.1039/JR9420000448
Adlercreutz H (2007) Lignans and human health. Crit Rev Clin Lab Sci 44(5–6):483–525. https://doi.org/10.1080/10408360701612942
Durazzo A, Zaccaria M, Polito A, Maiani G, Carcea M (2013) Lignan content in cereals, buckwheat, derived foods. Foods 2:53–63
Durazzo A, Turfani V, Azzini E, Maiani G, Carcea M (2013) Phenols, lignans and antioxidant properties of legume and sweet chestnut flours. Food Chem 140(4):666–671. https://doi.org/10.1016/j.foodchem.2012.09.062
Landete J (2012) Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health. Food Res Int 46(1):410–424. https://doi.org/10.1016/j.foodres.2011.12.023
Rodríguez-García C, Sánchez-Quesada C, Toledo E, Delgado-Rodríguez M, Gaforio J (2019) Naturally lignan-rich foods: a dietary tool for health promotion? Molecules 24(5):917. https://doi.org/10.3390/molecules24050917
Sok DE, Cui H, Kim M (2009) Isolation and boactivities of furfuran type lignan compounds from edible plants. Recent Pat Food Nutr Agric 1(1):87–95. https://doi.org/10.2174/2212798410901010087
Robinson R (1928) The relationship of some complex natural products to the simple and amino acids. Proc Univ Durh Philos Soc 8:14–59
Calvo-Flores FG, Dobado JA, Isac-García J, Martín-Martínez FJ (2015) Lignin and lignans as renewable raw materials: chemistry, technology and applications. Wiley, New York
Cunha WR, Silva MLA, Veneziani RCS, Ambrósio SR, Bastos JK (2012) Lignans: chemical and biological properties. www.intechopen.com.
Yousefzadi M, Sharifi M, Behmanesh M, Moyano E, Bonfill M, Cusido RM, Palazon J (2010) Podophyllotoxin: current approaches to its biotechnological production and future challenges. Eng Life Sci 10(4):281–292. https://doi.org/10.1002/elsc.201000027
Ward RS (2000) Recent advances in the chemistry of lignans. Stud Nat Prod Chem 1(24):739–798
Chunsriimyatav G, Hoza I, Valášek P, Skrovanková S, Banzragch D, Tsevegsuren N (2009) Anticancer activity of lignan from the aerial parts of Saussurea salicifolia (L.) DC. Czech J Food Sci 27(1):S256–S258. https://doi.org/10.17221/1097-cjfs
Lehraiki A, Attoumbré J, Bienaimé C, Matifat F, Bensaddek L, Nava-Saucedo E, Fliniaux MA, Ouadid-Ahidouch H, Baltora-Rosset S (2010) Extraction of lignans from flaxseed and evaluation of their biological effects on breast cancer MCF-7 and MDA-MB-231 cell lines. J Med Food 13(4):834–841. https://doi.org/10.1089/jmf.2009.0172
Shen W, Zhao Y, Chen H, Zhang T, Wu S, Liu P (2018) M3, a natural lignan xyloside, exhibits potent anticancer activity in HCT116 cells. Oncol Lett. https://doi.org/10.3892/ol.2018.9823
Lin RW, Tsai IL, Duh CY, Lee KH, Chen IS (2004) New lignans and cytotoxic constituents from Wikstroemia lanceolata. Planta Med 70:234–238
Zhou Y, Liu YE, Cao J, Zeng G, Shen C, Li Y, Zhou M, Chen Y, Pu W, Potters L, Shi YE (2009) Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res 15(16):5161–5169. https://doi.org/10.1158/1078-0432.ccr-09-0661
Bylund A, Saarinen N, Zhang JX, Bergh A, Widmark A, Johansson A, Lundin E, Adlercreutz H, Hallmans G, Stattin P, Makela S (2005) Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo. Exp Biol Med 230(3):217–223. https://doi.org/10.1177/153537020523000308
Luo J, Hu Y, Kong W, Yang M (2014) Evaluation and structure-activity relationship analysis of a new series of arylnaphthalene lignans as potential anti-tumor agents. PLoS ONE 9(3):e93516. https://doi.org/10.1371/journal.pone.0093516
Nakanishi T, Inatomi Y, Murata H, Shigeta K, Iida N, Inada A, Murata J, Farrera MAP, Iinuma M, Tanaka T, Tajima S, Oku N (2005) A new and known cytotoxic aryltetralin-type lignans from stems of Bursera graveolens. Chem Pharm Bull. https://doi.org/10.1002/chin.200533271
Chen JJ, Ishikawa T, Duh CY, Tsai IL, Chen IS (1996) New dimeric aporphine alkaloids and cytotoxic constituents of Hernandia nymphaeifolia. Planta Med 62(06):528–533. https://doi.org/10.1055/s-2006-957963
Moon SS, Rahman AA, Kim JY, Kee SH (2008) Hanultarin, a cytotoxic lignan as an inhibitor of actin cytoskeleton polymerization from the seeds of Trichosanthes kirilowii. Bioorg Med Chem 16(15):7264–7269. https://doi.org/10.1016/j.bmc.2008.06.032
Wu SJ, Wu TS (2007) Cytotoxic arylnaphthalene lignans from Phyllanthus oligospermus. ChemInform. https://doi.org/10.1002/chin.200704203
Tuchinda P, Kumkao A, Pohmakotr M, Sophasan S, Santisuk T, Reutrakul V (2006) Cytotoxic Arylnaphthalide lignan glycosides from the aerial parts of Phyllanthus taxodiifolius. Planta Med 72(01):60–62. https://doi.org/10.1055/s-2005-873141
Zhang YJ, Litaudon M, Bousserouel H, Martin MT, Thoison O, Léonce S, Dumontet V, Sévenet T, Guéritte F (2007) Sesquiterpenoids and cytotoxic lignans from the bark of Libocedrus chevalieri. J Nat Prod 70(8):1368–1370. https://doi.org/10.1021/np070124q
Xu LJ, Huang F, Chen SB, Zhang QX, Li LN, Chen SL, Xiao PG (2006) New lignans and cytotoxic constituents from Schisandra propinqua. Planta Med 72(02):169–174. https://doi.org/10.1055/s-2005-873199
Chen JJ, Chou ET, Duh CY, Yang SZ, Chen IS (2006) New cytotoxic tetrahydrofuran- and dihydrofuran-type lignans from the stem of Beilschmiedia tsangii. Planta Med 72(04):351–357. https://doi.org/10.1055/s-2005-916220
Li J, Zhang YJ, Jin BF, Su XZ, Tao YW, She ZG, Lin YC (2008) 1H and 13C NMR assignments for two lignans from the heartwood of Streblus asper. Magn Reson Chem 46:497–500
Habtemariam S (2003) Cytotoxic and cytostatic activity of erlangerins from Commiphora erlangeriana. Toxicon 41(6):723–727. https://doi.org/10.1016/s0041-0101(03)00048-5
Lee JS, Kim J, Yu YU, Kim YC (2004) Inhibition of phospholipase Cγ1 and cancer cell proliferation by lignans and flavans from Machilus thunbergii. Arch Pharm Res 27(10):1043–1047. https://doi.org/10.1007/bf02975429
Lin X, Switzer BR, Demark W (2001) Effect of mammalian lignans on the growth of prostate cancer cell lines. Anticancer Res 21(6A):3995–3999
Lee WJ, Park YH, Park SW, Yang EK, Kim JH (2003) Lignan from safflower seeds induces apoptosis in human promyelocytic leukemia cells. Prev Nutr Food Sci 8(2):113–118. https://doi.org/10.3746/jfn.2003.8.2.113
Hausott B, Greger H, Marian B (2003) Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells. J Cancer Res Clin Oncol 129(10):569–576. https://doi.org/10.1007/s00432-003-0461-7
Giridharan P, Somasundaram ST, Perumal K, Vishwakarma RA, Karthikeyan NP, Velmurugan R, Balakrishnan A (2002) Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis. Br J Cancer 87(1):98–105. https://doi.org/10.1038/sj.bjc.6600422
Gu JQ, Park EJ, Totura S, Riswan S, Fong HHS, Pezzuto JM, Kinghorn AD (2002) Constituents of the twigs of Hernandia ovigera that inhibit the transformation of JB6 murine epidermal cells. J Nat Prod 65(7):1065–1068. https://doi.org/10.1021/np020042w
Ito C, Itoigawa M, Ogata M, Mou XY, Tokuda H, Nishino H, Furukawa H (2001) Lignans as anti-tumor-promoter from the seeds of Hernandia ovigera. Planta Med 67(2):166–168. https://doi.org/10.1055/s-2001-11501
Takasaki M, Konoshima T, Komatsu K, Tokuda H, Nishino H (2000) Anti-tumor-promoting activity of lignans from the aerial part of Saussurea medusa. Cancer Lett 158(1):53–59. https://doi.org/10.1016/s0304-3835(00)00499-7
Navarro E, Alonso SJ, Trujillo J, Jorge E, Pérez C (2000) General behavior, toxicity, and cytotoxic activity of elenoside, a lignan from Justicia hyssopifolia. J Nat Prod 64(1):134–135. https://doi.org/10.1021/np9904861
Rickard SE, Yuan YV, Thompson LU (2000) Plasma insulin-like growth factor I levels in rats are reduced by dietary supplementation of flaxseed or its lignan secoisolariciresinol diglycoside. Cancer Lett 161(1):47–55. https://doi.org/10.1016/s0304-3835(00)00592-9
Saleem M, Kim HJ, Ali MS, Lee YS (2005) An update on bioactive plant lignans. Nat Prod Rep 22(6):696. https://doi.org/10.1039/b514045p
Messina F, Curini M, di Sano C, Zadra C, Gigliarelli G, Rascón-Valenzuela LA, Robles Zepeda RE, Marcotullio MC (2015) Diterpenoids and triterpenoids from the resin of Bursera microphylla and their cytotoxic activity. J Nat Prod 78(5):1184–1188. https://doi.org/10.1021/acs.jnatprod.5b00112
Chen JJ, Huang HY, Duh CY, Chen IS (2004) Cytotoxic constituents from the stem bark of Zanthoxylum Pistaciiflorum. J Chin Chem Soc 51(3):659–663. https://doi.org/10.1002/jccs.200400099
Jeong GS, Kwon OK, Park BY, Oh SR, Ahn KS, Chang MJ, Oh WK, Kim JC, Min BS, Kim YC, Lee HK (2007) Lignans and coumarins from the roots of Anthriscus sylvestris and their increase of caspase-3 activity in HL-60 cells. Biol Pharm Bull 30(7):1340–1343. https://doi.org/10.1248/bpb.30.1340
Wu SJ, Wu TS (2006) Cytotoxic arylnaphthalene lignans from Phyllanthus oligospermus. Chem Pharmaceut Bull 54(8):1223–1225. https://doi.org/10.1248/cpb.54.1223
Sriwiriyajan S, Sukpondma Y, Srisawat T, Madla S, Graidist P (2017) (−)-Kusunokinin and piperloguminine from Piper nigrum: an alternative option to treat breast cancer. Biomed Pharmacother 92:732–743. https://doi.org/10.1016/j.biopha.2017.05.130
Donoso-Fierro C, Tiezzi A, Ovidi E, Ceccarelli D, Triggiani D, Mastrogiovanni F, Taddei AR, Pérez C, Becerra J, Silva M, Passarella D (2014) Antiproliferative activity of yatein isolated from Austrocedrus chilensis against murine myeloma cells: cytological studies and chemical investigations. Pharm Biol 53(3):378–385. https://doi.org/10.3109/13880209.2014.922588
Wangteeraprasert R, Lipipun V, Gunaratnam M, Neidle S, Gibbons S, Likhitwitayawuid K (2012) Bioactive compounds from Carissa spinarum. Phytother Res. https://doi.org/10.1002/ptr.4607
Mukhija M, Dhar KL, Kalia AN (2014) Bioactive lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential. J Ethnopharmacol 152(1):106–112. https://doi.org/10.1016/j.jep.2013.12.039
Mulabagala V, Subbaraju GV, Ramani MV, DeWitt DL, Nair MG (2008) Lipid peroxidation, cyclooxygenase enzyme and tumor cell proliferation inhibitory lignans from Justicia species. Nat Prod Commun 3(11):1934578X0800301. https://doi.org/10.1177/1934578x0800301109
Su B, Zhu Q, Gao K, Yuan C, Jia Z (1999) Lignan and phenylpropanoid glycosides from Lancea tibetica and their antitumor activity. Planta Med 65(6):558–561. https://doi.org/10.1055/s-1999-14026
Gnabre J, Unlu I, Chang TC, Lisseck P, Bourne B, Scolnik R, Jacobsen NE, Bates R, Huang RC (2010) Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: structure–activity relationships. J Chromatogr B 878(28):2693–2700. https://doi.org/10.1016/j.jchromb.2010.08.005
Aimaiti S, Saito Y, Fukuyoshi S, Goto M, Miyake K, Newman DJ, O’Keefe BR, Lee KH, Nakagawa-Goto K (2019) Isolation, structure elucidation, and antiproliferative activity of butanolides and lignan glycosides from the fruit of Hernandia nymphaeifolia. Molecules 24(21):4005. https://doi.org/10.3390/molecules24214005
Kintzios SE (2006) Terrestrial plant-derived anticancer agents and plant species used in anticancer research. Crit Rev Plant Sci 25(2):79–113. https://doi.org/10.1080/07352680500348824
Kardono LBS, Tsauri S, Padmawinata K, Pezzuto JM, Kinghorn AD (1990) Cytotoxic constituents of the bark of Plumeria rubra collected in Indonesia. J Nat Prod 53(6):1447–1455. https://doi.org/10.1021/np50072a008
Novelo M, Cruz JG, Hernández L, Pereda-Miranda R, Chai H, Mar W, Pezzuto JM (1993) Cytotoxic constituents from Hyptis verticillata. J Nat Prod 56(10):1728–1736. https://doi.org/10.1021/np50100a011
Torrance SJ, Hoffmann JJ, Cole JR (1979) Wikstromol, antitumor lignan from Wikstroemia foetida var. oahuensis gray and Wikstroemia uva-ursi gray (thymelaeaceae). J Pharmaceut Sci 68(5):664–665. https://doi.org/10.1002/jps.2600680545
Lee SK, Cui B, Mehta RR, Kinghorn A, Pezzuto JM (1998) Cytostatic mechanism and antitumor potential of novel 1H-cyclopenta[b]benzofuran lignans isolated from Aglaia elliptica. Chem Biol Interact 115(3):215–228. https://doi.org/10.1016/s0009-2797(98)00073-8
Zhao CQ, Zhu YY, Chen SY, Ogihara Y (2011) Lignan glucoside from Sinopodophyllum emodi and its cytotoxic activity. Chin Chem Lett 22:181–184. https://doi.org/10.1016/j.cclet.2010.10.013
Chavez KJ, Feng X, Flanders JA, Rodriguez E, Schroeder FC (2011) Spirocyclic lignans from Guaiacum (Zygophyllaceae) induce apoptosis in human breast cancer cell lines. J Nat Prod 74(5):1293–1297. https://doi.org/10.1021/np100891y
Kim KH, Kim HK, Choi SU, Moon E, Kim SY, Lee KR (2011) Bioactive lignans from the rhizomes of Acorus gramineus. J Nat Prod 74(10):2187–2192. https://doi.org/10.1021/np200541m
Ye YQ, Xia CF, Li YK, Wu XX, Du G, Hu QF, Gao XM (2014) A New dibenzocyclooctadiene lignan from the stems of Schisandra neglecta and its cytotoxicities. Asian J Chem 26(7):1948–1950. https://doi.org/10.14233/ajchem.2014.15583
Suh WS, Kim KH, Kim HK, Choi SU, Lee KR (2015) Three new lignan derivatives from Lindera glauca (Sieboldet Zucc.) Blume. Helv Chim Acta 98(8):1087–1094. https://doi.org/10.1002/hlca.201500002
Kim KH, Moon E, Kim SY, Choi SU, Lee KR (2012) Lignan constituents of Tilia amurensis and their biological evaluation on antitumor and anti-inflammatory activities. Food Chem Toxicol 50(10):3680–3686. https://doi.org/10.1016/j.fct.2012.07.014
Jin H, Yin HL, Liu SJ, Chen L, Tian Y, Li B, Wang Q, Dong JX (2014) Cytotoxic activity of lignans from Justicia procumbens. Fitoterapia 94:70–76. https://doi.org/10.1016/j.fitote.2014.01.025
Trinh Thi Thanh V, Cuong Pham V, Doan Thi Mai H, Litaudon M, Guéritte F, Retailleau P, Nguyen VH, Chau VM (2012) Cytotoxic lignans from fruits of Cleistanthus indochinensis: synthesis of cleistantoxin derivatives. J Nat Prod 75(9):1578–1583. https://doi.org/10.1021/np3003832
Ren Y, Lantvit D, Deng Y, Kanagasabai R, Gallucci J, Ninh T, Chai H, Soejarto D, Fuchs J, Yalowich J, Yu J, Swanson S, Kinghorn A (2014) Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei. Planta Med. https://doi.org/10.1055/s-0034-1382432
Liu Y, Yang Y, Tasneem S, Hussain N, Daniyal M, Yuan H, Xie Q, Liu B, Sun J, Jian Y, Li B, Chen S, Wang W (2018) Lignans from Tujia ethnomedicine Heilaohu: chemical characterization and evaluation of their cytotoxicity and antioxidant activities. Molecules 23(9):2147. https://doi.org/10.3390/molecules23092147
Rajalekshmi DS, Kabeer FA, Madhusoodhanan AR, Bahulayan AK, Prathapan R, Prakasan N, Varughese S, Nair MS (2016) Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives. Bioorg Med Chem Lett 26(7):1767–1771. https://doi.org/10.1016/j.bmcl.2016.02.041
Maa Y, Wang H, Wang R, Meng F, Dong Z, Wang G, Lan X, Quan H, Liao Z, Chen M (2019) Cytotoxic lignans from the stems of Herpetospermum pedunculosum. Phytochemistry 164:102–110. https://doi.org/10.1016/j.phytochem.2019.05.004
Su GY, Wang KW, Wang XY, Wu B (2015) Bioactive lignans from Zanthoxylum planispinum with cytotoxic potential. Phytochem Lett 11:120–126. https://doi.org/10.1016/j.phytol.2014.12.004
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Mukhija, M., Joshi, B.C., Bairy, P.S. et al. Lignans: a versatile source of anticancer drugs. Beni-Suef Univ J Basic Appl Sci 11, 76 (2022). https://doi.org/10.1186/s43088-022-00256-6