Table 1 List of lignans isolated from plant with anticancer activity

9-OH-Pinoresinol

1

Saussurea salicifolia (L.) DC, Asteraceae

Chloroform fraction of ethanolic extract

Aerial parts

L5178Y

–

–

10 μg/mL

Ethanolic extract of the plant reduced the growth of leukemia mouse lymphoma cells to 23.8%. It looks like lignan 9-OH-pinoresinol is responsible for the activity which is well known from other plant sources

[30]

Anhydrosecoisolariciresinol

2

Linum usitatissimum, Linaceae

–

Seeds

MCF-7

100 µM

The isolated lignan causes 30% inhibition of cell growth as compared to control

[31]

4-O-(2′,3′,4′-tri-O-methyl-β-D-xylopyranosyl) diphyllin

3

Phyllanthus taxodiifolius, Phyllanthaceae

–

Aerial parts

HCT116

0.08 ± 0.03 µM

In vitro studies has been shown to inhibit the growth of a number of cancer cell. It shows strongest antiproliferative effect on HCT116 cells. The compound induces apoptosis in HCT116 cells by activating caspase-3 pathway and antiproliferative effect is due to promotion of microtubule depolymerization

[32]

( +)-Hinokinin

4

Wikstroemia lanceolata, Thymelaeaceae

Methanol

Stems and roots

P-388

1.54 µg/mL (ED₅₀)

Showed significant cytotoxic activity

[33]

Vitexin

5

Vitex negundo, Verbenaceae

Ethanol

Seeds

MCF-7, ZR-75-1, SK-BR-7, MDA-MB-231, MDA-MB-435s, PC-3, LNCaP and COC1

100 mg/kg

In vivo studies done using tumor xenograft models like MCF-7, MA782, MDA-MB-435s, and T47D xenografts for breast, PC-3 for prostate, HeLa cells for cervical, and HepG2 for liver xenograft

Vitexins (lignan mixture) has cytotoxic effects on MCF-7, ZR-75-1, SK-BR-7, MDA-MB-231, MDA-MB-435s, PC-3, LNCaP COC1 cancer cells. Vitexin induced antitumor effect and cytotoxic activity is exerted through proapoptotic process, which is mediated by a decreased Bcl-2/Bax ratio and activation of caspases

[34]

7-Hydroxymatairesinol (HMR)

6

Picea abies, Pinaceae

Acetone–water (9:1)

Heartwood

LNCaP human prostate cancer xenografts in athymic nude male mice

There is significant decrease in tumor volume. A control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. The diet supplemented with HMR has been shown to inhibit the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of non-growing tumors, and higher tumor cell apoptotic index compared with controls. Cell proliferation index was also decreased in mice receiving the 0.30% HMR diet when compared with mice receiving the control diet

[35]

6′-Hydroxy justicidin A, 6′-hydroxy justicidin B, justicidin B

7, 8, 9

Justicia procumbens, Acanthaceae

Ethanolic

Whole plant

K562

20, 43.9 and 45.4 µM

All the compounds significantly inhibited the growth of K562 cells by decreasing both proliferation and SOD activity and inducing apoptosis in dose-dependent manner. Activation of caspase-3 pathway suggests that these compounds induce apoptosis through caspase intrinsic or extrinsic pathway

[36]

Picropolygamain, Burseranin

10, 11

Bursera graveolens, Burseraceae

Methanol

Stem

HT1080

1.9, 5.5 µg/mL (ED₅₀)

Showed significant cytotoxic activity

[37]

(-)-Deoxypodophyllotoxin, (-)-yatein

12, 13,

Hernandia nymphaeifolia, Hernandiaceae

Methanol

Bark

P-388, KB16, A549, HT-29

< 1 µg/mI (ED₅₀)

Showed significant cytotoxic activity

[38]

Hanultarin, 1,4-O-Diferuloylsecoisolariciresinol

14, 15

Trichosanthes kirilowii, Cucurbitaceae

80% Aqueous methanol

Seeds

A549, SK-Mel-2, B16F1

3–13 µg/mL

Inhibitory effect on the polymerization of the actin cytoskeleton in normal epidermal keratinocyte (HaCaT cells) has been shown by compound Hanultarin as compared to those of the other isolates

[39]

Phyllanthusmin A

16

Phyllanthus oligospermus, Phyllanthaceae

Chloroform fraction of methanolic extract

Stems and roots

KB and P-388

2.24 µg/mL and 0.13 µg/mL

Showed significant cytotoxic activity

[40]

Cleistanthin A, Cleistanthin A methyl ether, Taxodiifoloside

17, 18, 19

Phyllanthus taxodiifolius, Euphorbiaceae

Ethanol fraction of methanol extract

Aerial parts

Five cultured mammalian cell lines. P-388, KB, Col-2, MCF-7 and Lu-1

Compounds showed GI₅₀ value in the range 10^–6–10^–9 M

Cleistanthin A, Cleistanthin A methyl ether has shown potent cytotoxic activity and Taxodiifoloside showed moderate activity

[41]

5-Methoxy-4-epipodophyllotoxin, 5-methoxypodophyllotoxin

20, 21

Libocedrus chevalier, Cupressaceae

Ethyl acetate

Bark

KB

45 µM and 11 µM

Both isolated lignans were also evaluated for their tubulin assembly inhibitory activity. 5-methoxy-4-epipodophyllotoxin inhibited the assembly of tubulin into microtubules with an IC₅₀ of 9 µM, whereas the IC₅₀ of 5-methoxypodophyllotoxin was 5 µM

[42]

Propinquanin B

22

Schisandra propinqua (Wall.), Schisandraceae

Chloroform

Stems

HL-60, Hep-G2, R- Hep-G2, KB, Bel-7402

7.15, 9.81, 14.00, 11.70, 18.81 µM

Cell cycle study and Hoechst 33,258 staining assay suggests that cytotoxic activity of compound may be due to induction of apoptosis

[43]

Beilschmin A,

Beilschmin B,

Beilschmin C

23, 24, 25

Beilschmiedia tsangii, Lauraceae

-

Stems

P-388 and HT-29

1.2 and 5.0 µg/mL

2.2 and 5.1 µg/mL

3.6 and 10.5 µg/mL

Showed significant cytotoxic activity

[44]

Magnolignan A 2-O-β-D-glucopyranoside, Strebluslignanol

26, 27

Streblus asper, Moraceae

Chloroform fraction of 75% ethanol

Heartwood

Hep-2 and Hep-G2

13.3 μM, 46.4 μM and 10.1 μM, 21.7 μM

Both lignans showed medium cytotoxic activity

[45]

Erlangerin A to D

2, 29, 30, 31

Commiphora erlangeriana, Burseraceae

Resin

EAhy926 and HeLa, L929 and RAW 264.7

68 ± 6, 40 ± 5, 90 ± 5 and 44 ± 9 µg/mL (EC₅₀)

23 ± 1.4, 4.0 ± 1.4, 68 ± 6 and 28 ± 0.3 (EC₅₀)

0.16 ± 0.09, 0.55 ± 0.007, 5.6 ± 1.5 (EC₂₅), and 0.97 ± 0.21 µg/mL (EC₅₀)

0.026 ± 0.007, 0.026 ± 0.009, 3.5 ± 1 µg/mL(EC₂₅), 0.11 ± 0.017 µg/mL (EC₅₀)

Erlangerins C and D were similar to podophyllotoxin on the basis of their structure and biological activity so may have same mechanism of action. They induced a concentration-dependent cytotoxicity in RAW 264.7 and cytostatic effect in HeLa, EAhy926, and L929 cells. But Erlangerins A and B suppressed cell viability at relatively higher concentrations when compared with Erlangerin C and D

[46]

Machilin A,

(-)-Sesamin,

Machilin G,

( +)-Galbacin

32, 33, 34, 35

Machilus thunbergii, Lauraceae

Dichloromethane

Bark

HCT-15, MCF-7 and A549

12.4, 12.4 and 7.9 µM

4.4, 3.4 and 11.0 µM

1.4, 2.7 and 8.3 µM

6.2, 7.9 and 7.9 µM

PLCγ1 plays a key role in proliferation and progression of human cancer. These compounds inhibit PLCγ1 and showed strong antiproliferative activity

[47]

Enterolactone, Enterodiol

36, 37

Mammalian lignans

LNCaP

57 mM and 100 mM

10–100 microM

Growth of prostate cancer cells were suppressed may be by hormonally dependent and independent mechanisms

[48]

Matairesinol

38

Carthamus tinctorius, Asteraceae

–

Seeds

HL-60

60 μM

DNA content histogram was analyzed by flow cytometry and it showed rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 μM matairesinol. It was concluded that cell death was due to the DNA damage and apoptosis

[49]

Nordihydroguaiaretic acid

39

Larrea tridentata DC. Coville, Zygophyllaceae

Resinous exudate

Bush

SW480

1.9 ± 0.5 µg

It caused time and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl_xl and an increase of the apoptotic index. It also induced a shift of the culture population to the G2/M phase of the cell cycle

[50]

Epiashantin

40

Artemisia absinthium L., Asteraceae

–

Warmwood

SW480

9.8 ± 4.5 µM

The compound caused a time and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl_xl and an increase of the apoptotic index

[50]

Arctigenin

41

Arctium lappa L., Asteraceae

–

Root

SW480

16.5 ± 8.5 µM

The compound caused a time and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl_xl and an increase of the apoptotic index

[50]

7′-Hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxylignan

42

Phyllanthus urinaria, Phyllanthaceae

Ethyl acetate

Whole plant

HEp-2

4.46 µM

7′-hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxylignan was capable of inhibiting telomerase activity and also could inhibit bcl₂ and activate caspase 3 and caspase 8 whose significance in the induction of apoptosis is well known

[51]

( +)-7′-Acetylpicropodophyllin, Epiyangambin

43, 44

Hernandia ovigera L., Hernandiaceae

Ethyl acetate

Twigs

JB6

0.15 and 0.4.2 µg/mL

Significant inhibition of the transformation of murine epidermal JB6 cells,

[52]

Deoxypodophyllotoxin,

6,7 Demethylenedeoxypodophyllotoxin,

1,2,3,4-Dehydrodeoxypodophyllotoxin,

Dehydropodophyllotoxin,

Bursehernin,

Podorhizol,

Epimagnolin

12, 45, 46, 47, 48, 49, 50

Hernandia ovigera L., Hernandiaceae

Seeds

Epstein-Barr virus early antigen activation (EBV-EA) induced by 12-O tetradecanoylphorbol 13-acetate (TPA) in Raji cells

550 mol ratio/32 pmol TPA,

510

520

470

470

480

590

Inhibitory effects on EBV activation has been shown by all isolated compounds

[53]

Arctiin,

Arctigenin

51, 41

Saussurea medusa, Composite

Methanol

Aerial parts

Two stage skin carcinogenesis model using DMBA (7,12-dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoyl phorbol-13-acetate)

Both lignans arctiin and arctigenin exhibited a significant inhibitory effect on the tumor promotion induced by DMBA and TPA by both topical application and oral administration. When both compounds were administered orally reduction in papillomas per mouse at 15 weeks of promotion in case of arctigenin was 4.2 ± 0.1 and Arctiin 4.0 ± 0.2, and at 20 weeks of promotion arctigenin was 6.1 ± 0.1 and Arctiin was 6.1 ± 0.2

[54]

Elenoside

52

Justicia hyssopifolia L., Acanthaceae

Ethanolic

Leaves

CCRFCEM, K-526, MOLT-4, RPMI-8226

79–97% growth inhibition

10^–4 M

Elenoside was cytotoxic to leukemic cell lines (CCRFCEM, K-526, MOLT-4, RPMI-8226) at a concentration of 10^–4 M (79–97% growth inhibition). Elenoside does not show significant activity at concentration less than 10^–4

[55]

Secoisolariciresinol diglycoside

53

Linum usitatissimum, Linaceae

Ethanolic

Seeds

Female Sprague–Dawley rats

2.93 mmoles/g

Increased plasma insulin-like growth factor I (IGF-I) concentrations are associated with increased breast cancer risk. Secoisolariciresinol diglycoside reduced plasma IGF-I levels. It inhibit

Mammary tumor development in rats

[56]

Phillygenol

Phillyroside

Phillygenoldiglycoside

54, 55, 56

Lancea tibetica, Mazaceae

SMMC-7721, HeLa, V79, B16

Phillygenol has shown strong cytotoxic activity on the tested cell lines whereas Phillyroside and Phillygenoldiglycoside had little effect on the proliferation of the tested cell lines

[57]

Podophyllotoxins

45, 46, 47…

Podophyllum peltatum, Podophyllum emodi, Podophyllum versipelle, Linum Juniperus

small-cell lung cancer (SCLC) dose: > 1 µg/mL (etoposide)

Disrupt the organization of the karyokinetic spindle single-strand and double-strand breaks in DNA through their interactions with DNA topoisomerase II induce cell cycle arrest in the G2-phase of the cell cycle

[17]

Ariensin

Burseran

Dihydroclusin diacetate

57, 11, 58

Bursera microphylla A. Gray, Burseraceae

Methanol

Resin obtained from the bark of the plant

RAW264.7, M12.C3.F6 murine cancer cell line (macrophages transformed by virus Abelson leukemia)

9.8, 0.4, 0.2 μM for all three isolated compounds in RAW264.7 and 2.5 μM for Dihydroclusin diacetate in M12.C3.F6

Dihydroclusin diacetate was shown to be active against both murine cancer cell lines while ariensin, burseran, were active against only RAW246.7 murine cell line only

[58]

(-)-Hinokinin

4

Zanthoxylum pistaciiflorum Hayata, Rutaceae

Methanol

Stem Bark

HT-29 cell line

3.52 µg/mL (ED₅₀ value)

Showed significant cytotoxic activity against HT-29 cell line

[59]

(-)-Deoxypodophyllotoxin,

Angeloylpodophyllotoxin,

Deoxypicropodophyllotoxin,

Picropodophyllotoxin

12, 59, 60, 61

Anthriscus sylvestris Hoffm., Umbelliferae

Methanol

Roots

HL-60

Compounds have an apoptosis-inducing effect in HL-60 cells and it was determined by caspase-3 activation and DNA fragmentation. Typical ladders of DNA fragmentation were observed when treated with compound angeloylpodophyllotoxin, picropodophyllotoxin at 1 mM and (-)-Deoxypodophyllotoxin at 0.01 mM

[60]

Phyllanthusmin A

62

Phyllanthus oligospermus, Phyllanthaceae

Chloroform fraction of methanol extract

Stems and roots

KB and P-388

2.24 and 0.13 µg/mL

Phyllanthusmin A showed significant cytotoxicity

[61]

(-)-Kusunokinin

63

Piper nigrum, Piperaceae

Dichloromethane

Fruits

MCF-7 and MDA-MB-468

1.18 and 1.62 µg/mL

This compound induced cell apoptosis and drove cells toward the G2/M phase which is determined by cell studies. It also decreases topoisomerase II and Bcl-2. There is increase in p53, p21, bax, cytochrome c, and caspase-8, -7, and -3 activities, except caspase-9. This shows that kusunokinin has potent anticancer activity through the extrinsic pathway and G2/M phase arrest

[62]

Yatein

13

Austrocedrus chilensis, Cupressaceae

Methanol

Heartwood

P3X63-Ag8.653

Yatein exhibited potent cytotoxicity, inducing 75% cell death at 25 mg/mL after 24 h of treatment

Yatein showed toxicity in P3X cells in a dose-dependently. In cells that survived to yatein treatment, the microtubular apparatus was altered, as determined by immunofluorescence techniques, and SEM and TEM analyses displayed changes in morphological and ultrastructural level. There was alteration in cell shape and membrane system was damaged

[63]

(-)-Carinol,

(-)-Carissanol,

and (-)-Nortrachelogenin

64, 65, 66

Carissa spinarum L., Apocynaceae

Methanol

Stem

MCF7 and A549

< 1 µg/mL

11.0 and 17.4 µg/mL

29.0 and 88.3 µg/mL

The most active lignan was (-)-carinol and (-)-carissanol was more potent than (-)-nortrachelogenin

[64]

Sesamin,

Kobusin,

4′O Demethyl magnolin

67, 68

Zanthoxylum alatum, Rutaceae

Petroleum ether

Stem bark

A549 and MIA-PaCa

37.46 ± 1.097 and 34.04 ± 1.7621

34.71 ± 2.331 and 32.86 ± 2.0271

26.47 ± 1.871 and 26.47 ± 1.871 mg/mL

Cytotoxic activity has been shown by all three isolated lignans in different ranges. 4′O dimethyl magnolin was the novel bioactive compound from a plant source and found to be most active. In apoptosis study, treatment caused typical apoptotic morphological changes. It enhances the apoptosis at IC₅₀ dose (21.72 mg/mL) on MIA-PaCa cell line. This compound induce apoptosis as the mechanism of cell death

[65]

Justirumalin

69

Justicia neesii, Acanthaceae

MCF-7, AGS

42.8 and 42.1%, inhibition, respectively

25 μg/mL

Justirumalin inhibited human stomach and breast cancer cells

[66]

Justicidin E,

Simplexolin

70

Justi caorbiculata, Acanthaceae

MCF-7, SF-268, CNS, NCI-H460, HCT-116 and AGS

25 μg/mL

Justicidin E inhibited the proliferation of lung, breast and colon cancer cell lines with inhibition values ranged between 40 and 53% and simplexolin gave 40–50% inhibition against lung, breast, colon, and CNS cancer cell lines when tested at 25 µg/mL

[66]

Sylvatesmin

72

Lancea tibetica Hook. f. et Thoms, Scrophulariaceae

Methanol

Whole plant

B16, SMMC-7721, Hela

40.4 ± 1.4 mg/mL, 113.4 ± 2.16 mg/mL, 127.9 ± 3.20 mg/mL

25 µg/mL

Sylvatesmin exhibited the effective antitumor activity, especially on B16 cells

[67]

Gomisin N

73

Schisandra chinensis (Turcz.)

Baill., Schisandraceae or Magnoliaceae

Dichloromethane

Ripe berries

HT-29

43 µM

Effective against colorectal proliferative processes

[68]

Epieudesmin

74

Hernandia nymphaeifolia (Presl) Kubitzki, Hernandiaceae

CH₃OH/CH₂Cl₂ (1:1) extract

Fruits

A549, MCF-7 and HER2, MDA-MB-231

5.7 µM, 8.1 µM, 231 8.2 µM

Compounds displayed significant anti proliferative activity

[69]

Podophyllotoxins, Diphyllin, Etoposide (VP–16), teniposide

12, 75, 76, 77

Podophyllum peltatum, Berberidaceae

Whole plant

P-388, HT-29, A-549 and MEL-28

This bioactive lignan is very effective on small cell lung cancer, malignant lymphoma, and testicular carcinoma

It is also potent on Wilms tumors, ovarian cancer, brain tumors, urinary tract cancer, etc.

[70]

Liriodendrin

78

Plumeria rubra, Apocynaceae

Water soluble fraction of methanolic extract

Stem bark

P-388 murine lymphocytic leukemia and human cancer cell types (fibrosarcoma, melanoma, breast, lung, colon and KB)

P-388—2.4 µg/mL

Fibrosarcoma—98.9 µg/mL

Melanoma—19 µg/mL

Breast cancer—30 µg/mL

Lung cancer—6.0 µg/mL

Colon cancer—16 µg/mL

KB—6.0 µg/mL (ED₅₀ values)

Exhibit cytotoxic activity

[71]

5- Methoxydehydro podophyllotoxin,

dehydro-β-peltatin methyl ether,

Dehydropodophyllotoxin,

Deoxydehydropodophyllotoxin,

Yatein,

4′-Demethyldeoxypodophyllotoxin,

Isodeoxypodophyllotoxin,

Deoxypicropodophyllin,

β-apopicropodophyllin

79, 80, 47, 81, 13, 82, 83, 60, 84

Hyptis verticillata, Lamiaceae

Chloroform

Aerial parts

P-388, HT-low, KB,

A43l, ZR-75-1, LNCaP and U373

4.0, 15.6, 6.0, 6.2, > 20, 11.6 and 16.3 µg/mL

1.8, 3.4, 2.2, > 20, > 20, 3.2, and 5.9 µg/mL

 > 5, 9.7, 5.0, > 20, > 20, 11.7 and > 20 µg/mL

 > 5, > 20, 11.4, 6.2, > 20, 11.6 and > 20 µg/mL

0.4, 0.07, 0.08, > 20, 0.5,

0.16, and 0.3 µg/mL

0.005, 0.01, 0.01, 0.08, 2.1, 0.02 and 0.1 µg/mL

 > 20, 10.7, 6.7, 6.2, 13.2, 12.0 and 2.9 µg/mL

0.1, 0.2, 0.1, > 20, 0.6, 0.2 and 0.1 µg/mL

0.002, 0.003, 0.05, 4.3, 2.0, 0.01 and 0.001 µg/mL. (ED₅₀ values)

[72]

Wikstromol

85

Wikstroemia foetida var.oahuensis and Wikslroemia uwa-ursi Gray Thymelaeaceae

Chloroform fraction of ethanolic extract

Whole plant

P-388 Iympho cyticleukemia (3PS) test system

16, 10, 4, 2, and 1 mg/kg

Wikstromol demonstrate activities of 154, 146, 137, 141, and 130% test/control at dose of 16, 10, 4, 2, and 1 mg/kg, respectively

[73]

4′-Demethoxy-3′,4′-methylenedioxy-methyl rocaglate

86

Aglaia elliptica Bl., Meliaceae

Chloroform

Stem

HT-1080, KB, A431, LNCaP, ZR-75-1, and U373, BCl

10.0, 6.0, 10.0, 2.0, 2.0, 0.8, 0.9 ng/mL

Antitumor potential of compound was performed with female Balb/c athymic nude mice. Compound significantly inhibited the growth of BC1 cells in culture. The growth of tumor was retarded by treatment with isolated compound during the first 23 days of the study, but after that tumor growth paralleled to the control group

This compound acts by cytostatic mechanism, rather than inducing necrosis or apoptosis. Cells were transiently blocked in the G1/G0 phases of the cycle, and this may be due to inhibition of protein biosynthesis

[74]

4,5-Didemethylpodophyllotoxin 7′-O-b-D-glucopyranoside

87

Sinopodophyllum emodi, Berberidaceae

n-butanol

Roots and rhizomes

Hela, K562, SH-SY5Y and CNE

Compound showed cytotoxicity against four human cancer cell lines

[75]

Ramonanin A

Ramonanin B

88, 89

Guaiacum officinale, Zygophyllaceae

Chloroform

Heartwood

MD-MBA 231

18 μM

The ramonanins exhibit cytotoxic activity against human breast cancer cell lines with an IC₅₀ value of 18 μM and induce cell death via apoptotic mechanisms

Ramonanin A-treated MD-MBA 231 cells showed characteristic features of apoptotic cell death, which appeared in a time and dose-dependent manner and cell cycle distribution was monitored via flow cytometry using fluorescence-activated cell sorting. It was noted that the ramonanins strongly disrupt cell cycle progression at the G1/S phase transition

[76]

Ligraminol A,

Ligraminol C,

Ligraminol D

90, 91, 92

Acorus gramineus, Araceae

Methanol

Rhizomes

A549, SK-OV-3, SK-MEL-2

6.92, 9.44, and 4.53 μM

Compounds showed weak inhibitory activity against various cancerous cell lines. Study has also been performed to check whether the cytotoxicity was selective between tumor and normal cells. For this compounds were evaluated for normal human cell line, HUVEC. This was noted that cytotoxicity of isolated compounds was higher against tumor cells than normal cells. Ligraminol A showed the highest selective cytotoxicity against the SK-MEL-2 cell

[77]

Neglignan H

93

Schisandra neglecta, Schisandraceae

Ethyl acetate layer of 70% aqueous acetone

Stem

NB4, A549 and MCF7

8.1, 7.4 and 6.7 µM

[78]

Linderanosides A and B

94, 95

Lindera glauca, Lauraceae

Methanolic

Twigs

A549

20.86 ± 0.94, 21.85 ± 0.61 µM

[79]

Tiliamuroside,

Schizandriside

96, 97

Tilia amurensis Rupr., Tiliaceae

Methanolic

Trunk

A549, SK-OV-3, SK-MEL-2, and HCT-15

7.32, 8.89, 7.84, and 6.18 μM

6.90, 5.88, 3.26, and 6.65 μM

cytotoxic activity of compounds against the tested cell lines were due to absence of a methoxy group at C-3 in the aryl-tetralin type lignan as indicated by the results

[80]

Pronaphthalide A, Procumbenoside J, 6′-hydroxyl justicidin A, 6′-hydroxyl justicidin B, Tuberculatin

98, 99, 100, 101, 102

Justica procumbens, Acanthaceae

Ethanol

Whole plants

Human LoVo and BGC-823

0.03–10.0 μM,

[81]

Cleistantoxin

103

Cleistanthus indochinensis, Euphorbiaceae

Dichloromethane

Fruits

KB, MCF-7, MCF-7R

0.022, 0.036, 0.014 μM

Cleistantoxin had strong activity against KB cells also showed significant activity against MCF-7 and MCF-7R

[82]

Phyllanthusmin D

104

Phyllanthus poilanei, Phyllanthaceae

Chloroform fraction of methanol extract

Air-dried leaves, twigs, flowers, and fruits

HT-29

170 nM

Compound showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice

5 μM

Cytotoxic effects of phyllanthusmin D were by inducing tumor cell apoptosis through activation of caspase-3. DNA topoisomerase IIα activity was not inhibited

Treatment of HT-29 cells with phyllanthusmin D for 72 h resulted in 28.2% or 30.3% of HT-29 cells undergoing early apoptosis, respectively,

[83]

Heilaohulignan C

105

Kadsura coccinea, Schisandraceae

80% ethanol

Roots

HepG-2, BGC-823 and HCT-116

9.92, 16.75 and16.59 µM

heilaohulignan C showed good cytotoxicity in HepG-2 cancer cells and weak cytotoxicity against BGC-823 and HCT-116 cancer cells

[84]

(-)-Cubebin

106

Piper cubeba, Piperaceae

Acetone

Seeds

A549, K562, SiHa, KB

8.30 ± 0.16, 8.66 ± 0.43, 8.16 ± 0.41 µM

[85]

Hedyotol-B

107

Herpetospermum pedunculosum, Cucurbitaceae

Ethyl acetate

Stems

SGC7901, A549

1.7 ± 0.1 and 6.1 ± 0.5 μM

Hedyotol-B displayed potent inhibitory effect against gastric and lung carcinoma

[86]

Bizanthplanispine A and B, Zanthpodocarpin A and B, Planispine A

108, 109, 110, 111, 112

Zanthoxylum planispinum Sieb., Rutaceae

95% aqueous MeOH

Roots

Hela, HL-60, PC-3

Bizanthplanispine A and B, zanthpodocarpin A and B showed significant reduction in the proliferation of Hela with IC₅₀ values ranging from 15.00 to 26.44 µg/mL. Planispine A showed the strongest inhibition on the growth of HL-60 and PC-3 with IC₅₀ values of 4.90 and 23.45 µg/mL

All isolated compounds showed inhibitory effect on different cancer cell lines

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