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Bhuia, M.S.; Wilairatana, P.; Chowdhury, R.; Rakib, A.I.; Kamli, H.; Shaikh, A.; Coutinho, H.D.M.; Islam, M.T. Anticancer Potentials of the Lignan Magnolin. Encyclopedia. Available online: https://encyclopedia.pub/entry/43458 (accessed on 15 December 2025).
Bhuia MS, Wilairatana P, Chowdhury R, Rakib AI, Kamli H, Shaikh A, et al. Anticancer Potentials of the Lignan Magnolin. Encyclopedia. Available at: https://encyclopedia.pub/entry/43458. Accessed December 15, 2025.
Bhuia, Md. Shimul, Polrat Wilairatana, Raihan Chowdhury, Asraful Islam Rakib, Hossam Kamli, Ahmad Shaikh, Henrique D. M. Coutinho, Muhammad Torequl Islam. "Anticancer Potentials of the Lignan Magnolin" Encyclopedia, https://encyclopedia.pub/entry/43458 (accessed December 15, 2025).
Bhuia, M.S., Wilairatana, P., Chowdhury, R., Rakib, A.I., Kamli, H., Shaikh, A., Coutinho, H.D.M., & Islam, M.T. (2023, April 25). Anticancer Potentials of the Lignan Magnolin. In Encyclopedia. https://encyclopedia.pub/entry/43458
Bhuia, Md. Shimul, et al. "Anticancer Potentials of the Lignan Magnolin." Encyclopedia. Web. 25 April, 2023.
Anticancer Potentials of the Lignan Magnolin
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This entry is adapted from the peer-reviewed paper 10.3390/molecules28093671

Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways.

lignan magnolin biological sources pharmacokinetic profile cancer cell lines

1. Introduction

Natural remedies are becoming increasingly prevalent worldwide as conventional or supplementary treatments for curable and incurable diseases and for encouraging health and disease prevention [1]. Due to their negligible side effects and good safety records, they are widely used in various diseases as effective therapeutic routes [2]. Lead compounds are abundant in plants and are used in drug discovery. Most (60–70%) of the antibacterial and anticancer medications used in clinical settings are natural compounds or their derivatives [3][4].
Naturally occurring lignans are a group of secondary metabolites that are found in a variety of sources, such as seeds, nuts, cereals, vegetables, and fruits. Lignans serve a range of purposes in plants, and their multifaceted functions are significant for various organisms, including humans [5][6][7]. They are mainly liable for the defense mechanism and are distinguished by the presence of two terminal phenyl groups in their chemical structure [8]. Phytochemicals that belong to the lignan class exhibit diverse biological features, including antioxidant, anti-inflammatory, antiestrogenic, anticarcinogenic, and antitumor activities [9][10]. Several epidemiological studies have suggested that lignans may lower the risk of cardiovascular disease. However, the impact of lignans on other chronic ailments, such as breast cancer, is still debated [11]. Additionally, the dietary intake of lignans has been linked with a diminished risk of other types of cancer, including colon cancer, gastric adenocarcinoma, and esophageal carcinoma. However, there have been very few human studies conducted on this topic [12]. The scientific community has previously mentioned the discovery and development of lignan derivatives for the creation of anticancer therapeutics. Examples of such drugs include etoposide, teniposide, and etopophos [13].
Magnolin is a lignan (C23H28O7, Figure 1), chemically known as (3S,3aR,6S,6aR)-3-(3,4-dimethoxy phenyl)-6-(3,4,5-tri methoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c] furan, that has been isolated from the Magnolia genus [14][15], which is a large genus of about 210 flowering species in the family Magnoliaceae [16], and has been shown to have health-enhancing properties in in vivo and in vitro test systems [17][18][19][20][21][22][23][24]. Magnolin exhibits various pharmacological activities, including anti-oxidative, anti-inflammatory, and vasodilatory effects. It has also been found to have protective effects against contrast-induced nephropathy and has been shown to inhibit the migration and invasion of lung cancer cells [21][23]. Additionally, magnolin has been found to be capable of suppressing cell proliferation and transformation by suppressing the ERKs/RSK2 signaling pathways and impairing the G1/S cell-cycle transition [25]. 
Figure 1. (a) Two-dimensional chemical structure of magnolin and (b) different pharmacological activities of magnolin based on literature.

2. Botanical Sources

Medicinal plants are considered significant resources for discovering novel drugs worldwide [26][27]. They hold cultural and economic importance to local communities and have been utilized in traditional and popular medicine as well as in the development of pharmaceuticals [28][29]. The commercial and scientific interest in medicinal plants as a source of primary materials for the herbal pharmaceutical industries is increasing rapidly due to the growing global demand [30]. The World Health Organization (WHO) reports that a significant proportion of individuals in developing countries (70–95%) rely on medicinal plants for their primary healthcare needs. However, despite their widespread use, only a small fraction (15%) of medicinal plants worldwide has been analyzed to measure their potential therapeutic benefits based on their phytochemical and phytopharmacological properties [31]. Magnolin, a biologically active compound, has been extracted from plants of the Magnolia genus [15]. Three species of magnolia, including Magnolia denudata, Magnolia sprengeri, and Magnolia biondii, have been recognized in the pharmacopoeia and are known for their therapeutic benefits [22]. The compound source is a component of the flowers, leaves, seeds, roots, and aerial portions of numerous species, according to accounts in the literature. The botanical origins of this lignan are shown in Table 1.
Table 1. Biological sources of magnolin.
Plant Name Plant Part References
Magnolia fargesii Flower buds [17][32]
Zanthoxylum simulans Bark [33]
M. biondii Flower buds [34][35][36]
Pseuderanthemum carruthersii Root [37]
M. officinalis Flower buds [38]
M. sargentiana and M. sprengeri - [22]
Castilleja tenuiflora Aerial part of roots [39]
Astrantia major Fruits [40]
Artemisia gorgonum Webb Leaves and flowers [24]
Acorus calamus - [41]
Rollinia mucosa Seeds [42]
M. denudata Flowers [43][44]
M. kobus Flower buds, bark [45][46]
M. salicifolia Flower buds [45]
Licaria armeniaca Trunk wood, fruits [47][48]
Achillea holosericea. Aerial parts [49]
Annona pickelii Leaves [50]
M. liliflora Leaves [51]
A. gypsicola Aerial parts and roots [52][53]
Z. alatum Seeds [54]
Hernandia ovigera Leaves [55]
Physalis peruviana Fruits [56]

3. Cellular and Molecular Anticancer Mechanisms of Magnolin

New precision medicine treatments for cancer are developed by utilizing information obtained from changes that occur at the molecular level in cancer genes and their associated signaling pathways. These days, it is widely acknowledged that signaling pathways and molecular networks play crucial roles in carrying out and regulating vital cellular processes that promote cell survival and growth and are hence largely responsible for the development of cancer as well as its potential treatment [57]. In cancer, two pathways, namely, the PI3K/AKT/mTOR signal transduction pathway and the Ras/MEK pathway, are commonly activated or mutated [58]. These pathways are closely interlinked in transmitting signals from receptor tyrosine kinases (RTKs) to intracellular effector proteins and cell cycle regulators, thus regulating upstream cellular signals [59]. Some other important signaling pathways that develop cancer and can be the target of therapeutic development include cell cycle, Hippo signaling [60], Notch signaling [61], Myc signaling [62][63], oxidative stress response/Nrf2 [64][65], TGFb signaling [66], β-catenin/Wnt signaling [67], and p53 signaling pathways [68]. CDK4/6 inhibitors (CDK4/6i) have made significant advancements in cancer treatment among all the signaling pathways targeting CDK4/6 activation [69].
Due to the growing number of deaths caused by cancer, it is essential to develop therapeutic strategies that have fewer cytotoxic side effects and are less prone to resistance. Natural compounds have been found to possess multiple beneficial activities, such as promoting overall health and providing cancer treatment [70]. Natural products have demonstrated preferential advantages against cancer cells when compared to normal cells. Additionally, their chemical structures can serve as models for the development of innovative drugs [70][71]. Using these models, drugs can be formulated that offer comparable or superior benefits to those provided by natural products. Moreover, these drugs may have fewer side effects and lower chances of resistance compared to the original natural products [72][73].
According to various studies in the documented literature on magnolin’s anticancer action, this therapeutic substance may prevent cancer by inhibiting the cell cycle, preventing metastasis, inducing apoptosis, and suppressing cell proliferation and migration [74] (Figure 2). The effective dose and the mechanism of action may differ depending on the kind of cancer (Table 2). Furthermore, the following provides comprehensive information on magnolin’s anticancer mechanism (Figure 2).
Molecules 28 03671 g003 550
Figure 2. Anticancer mechanisms of magnolin.
Table 2. Pharmacological mechanisms of magnolin involved in its anticancer activities.
Type of Cancer Experimental Model/
Cell Line		 Tested
Concentrations		 Efficacy, IC50
(Exposure Time)		 Anticancer Effects and Mechanisms Reference
Breast cancer MDA-MB-231 20 and 50 µM 30.34 µM (24 h) ↓MEK1/2, ↓ERK1/2, ↓CDK1, ↓BCL2, ↓MMP 2 and 9, ↑CASPASES3 and 9
↓proliferation, ↓invasion, ↑apoptosis		 [75]
MDA-MB-231 10, 20, 40, 60, 80, and 100 µM - ↓mRNA expression, ↓PTHrP, ↓MMP9, ↓cathepsin K, ↑RANKL/OPG ratio
↓bone loss and bone-resorbing activity		 [76]
- MCF-7 100 µg/mL - ↑cytotoxicity [37]
Lung cancer JB6CL41, NCI-H1975 and A549 15, 30, and 60 µM - ↓ERK1/2, ↓MMP2, ↓MMP9, ↓RSK2, ↓migration, ↓invasion [77]
NIH3T3, A549 15, 30, and 60 µM - ↓ERK1, ↓ERK2, ↓RSK2, ↓ATF1, ↓AP1, ↓proliferation, ↓migration [78]
Hepatocellular carcinoma BEL-7402 and SK-HEP1 25, 50, 75 100, and 125 μM - ↓MEK, ↓PI3K, ↓AKT,
↓proliferation		 [79]
Ovarian cancer TOV-112D 15, 30, and 60 µM - ↓ERK1, ↓ERK2, ↑P16Ink4a, ↑P27Kip1, ↓G1 and G2/M phase, ↓proliferation [25]
TOV-112D - 16 nM 68 nM ↓ERK1, ↓ERK2, ↓ATF1, ↓RSK2
↓proliferation		 [80]
Prostate cancer PANC-1 - 0.51 µM ↓MMP3, ↓proliferation, ↓migration [56]
PC3 and DU145 50 and 100 µM - ↓AKT, ↓BCL2, ↑BAX, ↑CASPASE3,
↑P53, ↑P21
↓G1, G2 phase, ↑apoptosis		 [23]
Pancreatic carcinoma MIA-PaCa - - ↑cytotoxicity [81]
Colon cancer HCT116 and HT29 - - ↓G2/M-phases, ↓proliferation [82]
Colorectal cancer HCT116 and SW480 10, 20, 30, and 40 µM - ↓LIF, ↓STAT3, ↓MCL1
↑ autophagy ↓cell cycle		 [83]
Arrows (↑ and ↓) show an increase or decrease in the obtained variables. MEK1/2: mitogen-activated protein kinase kinase 1 and 2; ERK1/2: extracellular signal-regulated kinase 1 and 2; CDK1: cyclin-dependent kinase 1; BCL2: B-cell lymphoma 2; MMP 2 and 9: matrix metalloproteinases 2 and 9; RSK2: ribosomal S6 kinase 2; ATF1: activating transcription factor 1; AP1: activator protein 1; PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; BAX: Bcl-2-associated X protein; LIF: leukemia inhibitory factor; STAT3: signal transducer and activator of transcription 3; MCL1: myeloid leukemia 1; P53: tumor protein P53; P21: tumor protein P21.

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Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Md. Shimul Bhuia , Polrat Wilairatana , Raihan Chowdhury , Asraful Islam Rakib , Hossam Kamli , Ahmad Shaikh , Henrique D. M. Coutinho , Muhammad Torequl Islam
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Update Date: 26 Apr 2023
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