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. 2018 Jul 30;2018:1826170. doi: 10.1155/2018/1826170

Table 3.

Anticancer effects of AGEs and extracts derived from the different aerial organs of A. muricata.

Cancers Cell lines Chemical compound or solvent Class Plant part Dose, IC50, ED50, GI50, LC50, IC25, and/or MIC Anticancer effects
Breast cancer MCF-7 Annomuricin A AGE Leaf ED50 > 1.0 μg/mL Cytotoxic activity [17]
Annomuricin B
Annomuricin C AGE Leaf —–— Cytotoxic activity [86]
Annomuricin E AGE Leaf ED50 = 1.45 μg/mL Cytotoxic activity [16]
Muricatocin C AGE Leaf —–— Cytotoxic activity [86]
Muricapentocin AGE Leaf ED50 = 1.90 μg/mL Cytotoxic activity [16]
Annomutacin AGE Leaf ED50 > 1.0 μg/mL Cytotoxic activity [43]
(2,4-cis)-10R-Annonacin-A-one + (2,4-trans)-10R-annonacin-A-one AGE Leaf ED50 = 5.70 × 10−1 μg/mL
Annohexocin AGE Leaf ED50 = 2.26 μg/mL Significant cytotoxic activity [34]
Muricatocin A AGE Leaf ED50 = 1.23 × 10−1 μg/mL Cytotoxic activity [44]
Muricatocin B AGE Leaf ED50 = 1.03 × 10−1 μg/mL
Annopentocin A AGE Leaf ED50 = 17.93 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 3.56 μg/mL
Annopentocin C AGE Leaf ED50 = 2.97 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 = 6.11 × 10−1 μg/mL
Murihexocin A AGE Leaf ED50 = 12.54 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 6.95 μg/mL
Murihexocin C AGE Seed ED50 = 3.8 μg/mL Cytotoxic activity [47]
Muricoreacin AGE Seed ED50 = 1.3 μg/mL
Muricatacin AGE Seed ED50 = 9.8 μg/mL Cytotoxic activity [48]
Isoannonacin AGE Seed IC50 = 1.1 × 10−2 μg/mL Cytotoxic activity [49]
Isoannonacin-10-one AGE Seed IC50 = 1.4 × 10−2 μg/mL
Goniothalamicin AGE Seed IC50 = 5.7 × 10−2 μg/mL
Gigantetrocin AGE Seed and/or leaf IC50 = 2.3 × 10−2 μg/mL
Gigantetrocin A AGE Seed ED50 = 5.3 × 10−1 μg/mL Cytotoxic activity [50]
Muricatetrocin A AGE Seed and/or leaf ED50 = 1.03 μg/mL Cytotoxic activity [17, 50]
Muricatetrocin B AGE Seed ED50 = 1.86 μg/mL
Gigantetrocin B AGE Seed ED50 = 5.3 × 10−1 μg/mL
cis-Annonacin AGE Seed IC50 = 1.18 μg/mL Cytotoxic activity [85]
cis-Annonacin-10-one AGE Seed IC50 = 2.9 × 10−1 μg/mL
cis-Goniothalamicin AGE Seed IC50 = 1.05 μg/mL
Arianacin AGE Leaf IC50 = 4.0 × 10−1 μg/mL
Javoricin AGE Leaf IC50 = 2.3 × 10−1 μg/mL
Hexane Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 49.92 ± 2.23 μg/mL Significantly reduced cell proliferation in cancer cells [31]
Ethyl acetate Extract Fruit Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 6.39 ± 0.43 μg/mL
Methanol Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 85.58 ± 3.55 μg/mL
——— Extract Leaf 0, 50, 100, 150, and 200 μg/mL; IC50 > 200 μg/mL Inhibited growth of cancer cells [23]
Ethanol (95%) Extract Leaf GI50 = 6.2 μg/mL Cytotoxic activity [45]
(+)-(3S,6S,7R,8S)-Periconone A Fungal strain Extract Leaf 0.01–10 μmol/mL Cytotoxic activity [38]
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide
MDA-MB-231 Hexane Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 38.72 ± 0.99 μg/mL Significantly reduced cell proliferation in cancer cells [31]
Ethyl acetate Extract Fruit Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 11.36 ± 0.67 μg/mL Significantly reduced cell proliferation in cancer cells [31]
Methanol Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 > 100 μg/mL
——— Extract Seed Doses: 50, 100, 150, and 200 μg/mL; IC50 > 200 μg/mL Inhibited the growth of cancer cells [23]
MDA-MB-231-pcDNA3 Methanol Extract Pericarp IC50 > 80 μg/mL Cytotoxic activity [24]
Methanol Extract Leaf
Methanol Extract seed
MDA-MB-231-BCRP clone 23 Methanol Extract Pericarp
Methanol Extract Seed
Methanol Extract Leaf
——— Ethanolic component (7,12-dimethylbenzeneanthracene (DMBA)) Extract Fruit Three groups of albino mice treated intragastrically by gavage for 6 weeks: 20 mg/mL/week of DMBA + 200 mg/mL/day of extract, 20 mg/mL/week of DMBA + 100 mg/mL/day of extract and 20 mg/mL/week of DMBA + 50 mg/mL/day of extract [139] Prevented DMBA-induced DNA damage [77, 139]
Leaves boiled in water Beverage Leaf A 66-year-old female who has been diagnosed with cancer used to boil 10–12 dry leaves in water for 5–7 minutes, 8 oz PO daily at that time Her metastatic breast cancer is still stable after 5 years on graviola and Xeloda after previously progressing on multiple lines of therapy [118]
MDA-MB-468 ——— Extract Leaf Doses: 5, 25, 50, or 100 μg/mL; IC50 = 4.8 μg/mLin vitro. In addition 200 mg/kg/35 week injected into the back of athymic mice in vivo Inhibited EGFR-overexpression and EGFR mRNA expression. Induced cell cycle arrest at the G0/G1 phase. Induced apoptosis through caspase-3 activation. In vivo, it inhibited the growth of MDA-MB-468 tumors implanted in athymic mice (32% growth inhibition). It also significantly reduced the protein expression of EGFR, p-ERK, and p-EGFR in tumors [23]
MDA Ethanol Extract Leaf IC50 = 248.77 μg/mL Cytotoxic activity [93]
SKBR3 Ethanol Extract Leaf IC50 = 202.33 μg/mL
T47D Ethanol Extract Fruit IC50 = 17.15 μg/mL Induced cytotoxicity and apoptosis [22]
Bladder cancer ECV-304 Ethanol Extract Twing 0.1–10 mg/mL in vitro, MIC = 2 mg/mL and 0.5 g/kg into albino mice in vivo [96] Cytotoxic activity against cancer cells in vitro and within reduction of time reaction in vivo [96]
Prostate cancer PC-3 Muricin J, K, or L AGEs Leaf Dose: 20 μg/mL (24 h) Antiproliferative activity against human cancer cells [29]
Annomuricin E AGE Leaf ED50 = 1.46 × 10−1 μg/mL Cytotoxic activity [16]
Muricapentocin AGE Leaf ED50 = 4.50 × 10−1 μg/mL
Annohexocin AGE Leaf ED50 = 0.0195 μg/mL Significant cytotoxic activity [34]
Annopentocin A AGE Leaf ED50 = 1.14 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 2.12 × 10−1 μg/mL
Annopentocin C AGE Leaf ED50 = 2.28 × 10−1 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 = 1.32 μg/mL
Murihexocin A AGE Leaf ED50 = 1.71 × 10−2 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 0.126 μg/mL
Murihexocin C AGE Fruit ED50 = 0.86 μg/mL Cytotoxic activity [47]
Muricoreacin ED50 = 0.025 μg/mL
Muricin M AGE fruit Dose: 20 μg/mL Antiproliferative activities against human prostate cancer cells [30]
Muricin N AGEs Leaf
Muricenin
——— Water Extract Leaf F344 male rats (≈200 g) were gavaged 30 mg/mL (10 rats) and 300 mg/mL (10 rats) and fed ad libitum alongside 10 control rats for two months Reduced prostate size in vivo, possibly through apoptosis [21]
Colorectal cancer HT-29 Annomuricin A AGE Leaf ED50 > 1.0 μg/mL Cytotoxic activity [17]
Annomuricin B AGE Leaf ED50 = 4.35 × 10−1 μg/mL
Annomuricin C AGE Leaf —–— Cytotoxic activity [86]
Muricatocin C
Annomuricin E AGE Leaf Doses: 1, 2, 4, 8, and 16 μg/mL [25]; ED50 = 6.68 × 10−2 μg/mL [16]; IC50: 5.72 ± 0.41 μg/mL (12 hr), 3.49 ± 0.22 μg/mL (24 hr), and 1.62 ± 0.24 μg/mL (48 hr) [25]. Induced toxicity against cancer cells [16, 25]. Suppressed proliferation of cancer cells and induced lactate dehydrogenase leakage, cell cycle arrest at G1 phase, and apoptosis mediated through activation of caspases 3/7 and 9. Also induced a time-dependent upregulation of Bax and downregulation of Bcl-2 at both the mRNA and protein level [25]
Muricapentocin AGE Leaf ED50 = 7.10 × 10−2 μg/mL Cytotoxic activity [16]
Annomutacin AGE Leaf ED50 > 1.0 μg/mL Cytotoxic activity [43]
(2,4-cis)-10R-Annonacin-A-one + (2,4-trans)-10R-annonacin-A-one AGE Leaf ED50 > 1.0 μg/mL
Annohexocin AGE Leaf ED50 = 0.78 μg/mL Significant cytotoxic activity [34]
Muricatocin A AGE Leaf ED50 = 1.56 μg/mL Cytotoxic activity [44]
Muricatocin B AGE Leaf ED50 = 1.66 μg/mL
Annopentocin A AGE Leaf ED50 = 1.63 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 1.64 μg/mL
Annopentocin C AGE Leaf ED50 = 1.24 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 < 10−2 μg/mL
Murihexocin A AGE Leaf ED50 = 3.00 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 2.30 μg/mL
Murihexocin C AGE Seed ED50 = 1.3 μg/mL Cytotoxic activity [47]
Muricoreacin AGE Seed ED50 = 0.57 μg/mL
Muricatacin AGE Seed ED50 = 14.0 μg/mL Cytotoxic activity [48]
Isoannonacin AGE Seed IC50 < 10−3 μg/mL Cytotoxic activity [49]
Isoannonacin-10-one AGE Seed IC50 = 1.8 × 103 μg/mL
Goniothalamicin AGE Seed IC50 = 1.1 × 10−3 μg/mL
Gigantetrocin AGE Seed and/or leaf IC50 < 103 μg/mL
Gigantetrocin A AGE Seed ED50 < 10−8 μg/mL Cytotoxic activity [50]
Muricatetrocin A AGE Seed and/or leaf ED50 < 10−8 μg/mL Cytotoxic activity [17, 50]
Muricatetrocin B AGE Seed ED50 = 2.8 × 10−5 μg/mL
Gigantetrocin B AGE Seed ED50 = 4.1 × 10−5 μg/mL
cis-Annonacin AGE Seed IC50 = 1.0 × 10−8 μg/mL Cytotoxic activity [85]
cis-Annonacin-10-one AGE Seed IC50 = 9.0 × 10−4 μg/mL
cis-Goniothalamicin AGE Seed IC50 = 5.3 × 10−3 μg/mL
Arianacin AGE Leaf IC50 = 4.4 μg/mL
Javoricin AGE Leaf IC50 = 1.8 μg/mL
Hexane Extract Leaf Doses: 10, 20, 40, and 80 μg/mL, IC50 = 14.93 ± 0.6 μg/mL (72 hr) Significantly reduced cell proliferation in cancer cells [26]
Ethyl acetate Extract Leaf Doses in vitro: 10, 20, 40, and 80 μg/mL [26]; 0.62, 1.25, 2.5, 5, 10, 20, 40, and 80 μg/mL [25]; IC50 = 4.29 ± 0.24 μg/mL (72 hr) [26]. Doses in vivo: 250 or 500 mg/kg into male Sprague-Dawley rats [25]. Induced significant cytotoxic effects, cell cycle arrest at G1 phase, and apoptosis. Treatment also caused excessive accumulation of ROS followed by disruption of MMP, cytochrome c leakage, and activation of the initiator and executioner caspases in cancer cells. In addition, it upregulated Bax and downregulated Bcl-2 proteins. Furthermore, treatment conspicuously blocked the migration and invasion of cancer cells [26]. In rats treated with azoxymethane to induce colorectal carcinogenesis. This extract reduced colonic aberrant crypt foci formation by 72.5% in vivo via downregulation of PCNA and Bcl-2 proteins and upregulation of Bax protein as well as an increase in the levels of enzymatic antioxidants and a decrease in the malondialdehyde level of the colon tissue homogenates, suggesting the suppression of lipid peroxidation [25]
Methanol Extract Leaf Doses: 10, 20, 40, and 80 μg/mL and IC50 > 100 μg/mL (72 hr) Significantly reduced the cell proliferation in cancer cells [26]
HCT-116 Hexane Extract Leaf Doses: 10, 20, 40, and 80 μg/mL and IC50 = 12.26 ± 0.42 μg/mL (72 hr)
Ethyl acetate Extract Leaf Doses: 10, 20, 40, and 80 μg/mL and IC50 = 3.91 ± 0.35 μg/mL (72 hr) In cancer cells, induced significant cytotoxic effects, cell cycle arrest at the G1 phase, and apoptosis as well as excessive accumulation of ROS followed by disruption of MMP, cytochrome c leakage, and activation of the initiator and executioner caspases. It also upregulated Bax and downregulated Bcl-2 protein. Furthermore, treatment conspicuously blocked the migration and invasion of cancer cells [26]
Methanol Extract Seed Doses: 10, 20, 40, and 80 μg/mL and IC50 > 100 μg/mL (72 hr) Significantly reduced cell proliferation in cancer cells [26]
HCT116 (p53+/+) Methanol Extract Pericarp IC50 > 100 μg/mL Cytotoxic activity [24]
Methanol Extract Leaf IC50 > 80 μg/mL
Methanol Extract Seed
HCT116 (p53−/−) Methanol Extract Pericarp
Methanol Extract Leaf
Methanol Extract Leaf
——— Ethanolic Extract Leaf 300 mg/kg into Wistar albino rats Showed potent anticancer activity through apoptosis and reduction of aberrant crypt foci formation [20]
Ethanol Extract Leaf 100 mg/kg body weight/4 weeks are administrated into Wistar rats In a rat model of Cycas-induced colorectal carcinogenesis, protected against some early events as monitored by histology and protein expression [140]
COLO-205 96% Ethanol [112] or ethanol soluble fraction leaf water extract contains 0.36% acetogenin (w/w) or 3.6 mg/g, and a 10 g water extract is equivalent to a 2 g ethanolic fraction [94]. Extract Leaf Doses in vitro: 400, 200, 100, 50, 25, 12.5, 6.25, 3.125, and 1.5625 mg/L, IC50 = 189.6 μg/mL (48 hr) [112]. Ex vivo, the colorectal cancer patients consumed either 300 mg of the extract, or maltose as a placebo, in the form of a capsule after breakfast [94]. Enhanced proapoptotic caspase-3 marker activity [112]. Ex vivo and clinical studies showed higher cytotoxicity in the supplemented group compared with the placebo group [94]
DLD-1 Ethanol soluble fraction leaf water extract contains 0.36% acetogenin (w/w) or 3.6 mg/g, and a 10 g water extract is equivalent to a 2 g ethanolic fraction. Extract Leaf Patients consumed either 300 mg of extract, or maltose as a placebo, in the form of a capsule after breakfast. Ex vivo and clinical studies showed higher cytotoxicity in the supplemented group compared with the placebo group [94]
HTC-8 (+)-(3S,6S,7R,8S)-Periconone A Fungal strain Extract Leaf Doses: 0.01–10 μmol/ml Cytotoxic activity [38]
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide Fungal strain Extract Leaf
Lung cancer A549 Annomuricin A AGE Leaf ED50 = 3.30 × 10−1 μg/mL Cytotoxic activity [17]
Annomuricin B AGE Leaf ED50 = 1.59 × 10−1 μg/mL
Annomuricin C AGE Leaf —–— Cytotoxic activity [86]
Muricatocin C AGE Leaf
Annomuricin E AGE Leaf ED50 = 1.12 × 10−1 μg/mL Cytotoxic activity [16]
Muricapentocin AGE Leaf ED50 = 1.93 × 10−1 μg/mL
Annomutacin AGE Leaf ED50 = 1.57 × 10−1 μg/mL Cytotoxic activity [43]
(2,4-cis)-10R-Annonacin-A-one + (2,4-trans)-10R-annonacin-A-one AGEs Leaf ED50 = 1.74 × 10−1 μg/mL
Annohexocin AGEs Leaf ED50 = 0.34 μg/mL Significant cytotoxic activity [34]
Muricatocin A AGE Leaf ED50 = 7.55 × 10−2 μg/mL Cytotoxic activity [44]
Muricatocin B AGE Leaf ED50 = 3.34 × 10−1 μg/mL
Annopentocin A AGE Leaf ED50 = 1.71 × 10−1 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 2.74 × 10−2 μg/mL
Annopentocin C AGE Leaf ED50 = 2.06 × 10−2 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 < 10−2 μg/mL
Murihexocin A AGE Leaf ED50 = 1.32 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 1.08 μg/mL
Murihexocin C AGE Seed ED50 = 1.1 μg/mL Cytotoxic activity [47]
Muricoreacin AGE Seed ED50 = 0.23 μg/mL
Muricatacin AGE Seed ED50 = 23.3 μg/mL Cytotoxic activity [48]
Isoannonacin AGE Seed IC50 = 9.6 × 10−3 μg/mL Cytotoxic activity [49]
Isoannonacin-10-one AGE Seed IC50 = 9.7 × 103 μg/mL
Goniothalamicin AGE Seed and/or leaf IC50 = 8.0 × 10−3 μg/mL
Gigantetrocin AGE Seed and/or leaf IC50 < 10−3 μg/mL
Gigantetrocin A AGE Seed ED50 = 8.1 × 10−3 μg/mL Cytotoxic activity [17, 50]
Muricatetrocin A AGE Seed and/or leaf ED50 = 1.4 × 10−1 μg/mL
Muricatetrocin B AGE Seed ED50 = 4.9 × 10−1 μg/mL
Gigantetrocin B AGE Seed ED50 = 2.5 × 10−1 μg/mL
cis-Annonacin AGE Seed IC50 = 2.3 × 10−1 μg/mL Cytotoxic activity [85]
cis-Annonacin-10-one AGE Seed IC50 = 3.5 × 10−1 μg/mL
cis-Goniothalamicin AGE Seed IC50 = 1.3 × 10−1 μg/mL
Arianacin AGE Leaf IC50 = 4.7 × 10−3 μg/mL
Javoricin AGE Leaf IC50 = 1.7 × 10−2 μg/mL
Ethyl acetate component Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50: 5.09 ± 0.41 μg/mL (72 hr) Selective cytotoxic effect against cancer cells and significant lactate dehydrogenase leakage and phosphatidylserine externalization demonstrated by fluorescence analysis. Treatment also elevated ROS formation, while attenuating MMP via upregulation of Bax and downregulation of Bcl-2. This was accompanied by cytochrome c release to the cytosol, which triggered activation of caspase-9 and caspase-3. These proapoptotic effects were accompanied by cell cycle arrest at the G0/G1 phase and suppression of NF-κB translocation from the cytoplasm to the nucleus [31]
Hexane Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 21.05 ± 0.42 μg/mL Significantly reduced cell proliferation in cancer cells [31]
Methanol Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 > 100 μg/mL
(+)-(3S,6S,7R,8S)-Periconone A Fungal strain Extract Leaf Doses: 0.01–10 μmol/mL Cytotoxic activity [38]
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide Fungal strain Extract Leaf
H-460 Ethanol Extract Tree/Leaf IC50 < 0.22 μg/mL Cytotoxic activity [95]
Ethanol (95%) Extract Pericarp GI50 = 4.0 μg/mL Cytotoxic activity [45]
NCI-H292 Methanol Extract Pericarp IC50: 24.94 ± 0.74 μg/mL Antiproliferative and cytotoxic activities towards cancer cells [113]
Leukemia (hematological malignancies) U-937 Annonacin A AGE Pericarp Doses: 0.1, 0.46, and 1.0 mg/mL Cytotoxic activity [46]
Annomuricin A AGE Pericarp
Methanol Extract Pericarp MEC > 1 mg/mL
Hexane Extract Leaf MEC = 1 mg/mL
Ethyle acetate Extract Stem MEC = 0.1 mg/mL
Ethyle acetate Extract Stem LC50 = 7.8 ± 0.3 μg/mL Cytotoxic activity [131]
Ethyle acetate Extract Stem IC50 = 10.5 ± 2.3 and/or 28.1 ± 13.0 μg/mL Cytotoxic activity [33]
Methanol Extract Stem IC50 = 60.9 ± 10.4 and/or 38.5 ± 8.6 μg/mL
Hexane Extract Stem IC50 = 18.2 ± 0.8 and/or 15.7 ± 5.1 μg/mL
K562 Ethanol Extract Leaf Doses in vitro: 0.625 mg/mL, 1.25 mg/mL, 2.5 mg/mL, and 5.0 mg/mL [19]; 0.1–10 mg/mL [96]; MIC = 7 mg/mL [96]. Dose in vivo: 0.5 g/kg into albino mice [96]. Showed cytotoxicity in vitro [19] and in vivo [96]. This was accompanied in vitro by significantly increased caspase-3 activity. Induction of apoptosis was confirmed by a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay [19]
HL-60 Ethanol Extract Root IC50 = 14 ± 2.4 μg/mL Induced apoptosis through loss of MMP and inhibited proliferation via G0/G1 cell cycle arrest [27]
Ethanol Extract Fruit/pericarp IC50 = 49 ± 3.2 μg/mL
Ethanol Extract Leaf IC50 = 9 ± 0.8 μg/mL
CCRF-CEM Methanol Extract Seed IC50 = 4.58 ± 0.25 μg/mL Induced cytotoxic, apoptosis, and cell cycle arrest [24]
Methanol Extract Leaf IC50 = 0.57 ± 0.02 μg/mL
Methanol Extract Seed IC50 = 0.36 ± 0.03 μg/mL
CEM/ADR5000 Methanol Extract Pericarp IC50 = 5.25 ± 0.38 μg/mL
Methanol Extract Leaf IC50 = 6.65 ± 0.22 μg/mL
Methanol Extract Leaf IC50 = 23.70 ± 1.64 μg/mL
Renal cancer A498 Annomuricin E AGE Leaf ED50 = 1.41 μg/mL Cytotoxic activity [16]
Muricapentocin AGE Leaf ED50 = 1.72 μg/mL
Annohexocin AGE Leaf ED50 = 2.36 μg/mL Cytotoxic activity [34]
Annopentocin A AGE Leaf ED50 = 6.07 × 10−1 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 3.79 × 10−1 μg/mL
Annopentocin C AGE Leaf ED50 = 2.58 × 10−1 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 = 1.22 × 10−1 μg/mL
Murihexocin A AGE Leaf ED50 = 2.51 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 4.92 μg/mL
Murihexocin C AGE Leaf ED50 = 2.5 μg/mL Cytotoxic activity [47]
Muricoreacin AGE Leaf ED50 = 0.71 μg/mL
Pancreatic cancer PACA Annomuricin E AGE Leaf ED50 = 2.42 × 10−2 μg/mL Cytotoxic activity [16]
Muricapentocin AGE Leaf ED50 = 5.03 × 10−2 μg/mL
PACA-2 Annohexocin AGE Leaf ED50 = 0.77 μg/mL Significant cytotoxic activity [34]
Annopentocin A AGE Leaf ED50 = 3.58 × 10−2 μg/mL Cytotoxic activity [32]
Annopentocin B AGE Leaf ED50 = 1.62 × 10−1 μg/mL
Annopentocin C AGE Leaf ED50 = 4.28 × 10−1 μg/mL
cis-Annomuricin-D-one + trans-annomuricin-D-one AGEs Leaf ED50 < 10−2 μg/mL
Murihexocin A AGE Leaf ED50 = 9.73 × 10−2 μg/mL Significant cytotoxic activity [15]
Murihexocin B AGE Leaf ED50 = 0.413 μg/mL
Murihexocin C AGE Leaf and/or stem ED50 = 0.49 μg/mL Cytotoxic activity [47]
Muricoreacin AGE Leaf and/or stem ED50 = 2.3 μg/mL
FG/COLO357 Powder without binders or fillers (capsule contents is suspended in DMSO (100 mg/mL DMSO) Extract Leaf Doses: 10–200 μg/mL.
IC50 = 200 μg/mL		 Induced cytotoxicity and necrosis by inhibiting cellular metabolism. In addition, it downregulated the expression of molecules related to hypoxia and glycolysis (i.e., HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) in cancer cells. Also, the motility of pancreatic cancer cells was decreased [28]
CD18/HPAF DMSO in vitro and H2O in vivo Extract Leaf Doses: 10–200 μg/mL, IC50 = 73 μg/mL in vitro. 50 mg/kg/35 days injected orthotopically in the pancreas of athymic nude mice Induced cytotoxicity and necrosis and inhibited cellular metabolism. In addition, it downregulates the expression of molecules related to hypoxia and glycolysis (i.e., HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) in cancer cells. After treatment, the motility of pancreatic cancer cells was decreased. It also caused 59.8% growth inhibition of pancreatic tumor induced in mice orthotopically implanted with CD18/HPAF cells [28]
Capan-1 Hexane Extract Seed IC25~7.8–8 μg/mL Inhibited cell proliferation and induced mild cytotoxicity in cancer cells [92]
DMSO Commercialized Extract Seed IC25~0.9–1.0 μg/mL
Hepatic cancer Hep G2 Muricin H AGE Seed IC50 = 9.51 × 10−2 μg/mL Exhibited significant activity in in vitro and cytotoxic assays against human hepatoma cell line [81]
Muricin I AGE Leaf IC50 = 5.09 × 10−2 μg/mL
cis-Annomontacin AGE Leaf IC50 = 2.98 × 10−1 μg/mL
cis-Corossolone AGE Seed IC50 = 1.65 × 10−1 μg/mL
Annocatalin AGE Leaf IC50 = 5.70 μg/mL
Annocatacin A AGE Leaf IC50 = 12.11 μg/mL Significant in vitro cytotoxic activity [80]
Annocatacin B AGE Seed IC50 = 3.35 × 10−2 μg/mL
Methanol Extract Pericarp IC50 > 80 μg/mL Cytotoxic activity [24]
Methanol Extract Seed
Methanol Extract Seed
Muricin A AGE Seed IC50 = 5.04 μg/mL Cytotoxic activity [82]
Muricin B AGE Seed IC50 = 1.78 μg/mL
Muricin C AGE Seed IC50 = 4.99 μg/mL
Muricin D AGE Seed IC50 = 6.60 × 10−4 μg/mL
Muricin E AGE Seed ———
Muricin F AGE Seed IC50 = 4.28 × 10−2 μg/mL
Muricin G AGE Seed ———
Muricatetrocins A & B AGE Seed IC50 = 4.95 × 10−2 μg/mL
Longifolicin AGE Seed IC50 = 4.04 × 10−4 μg/mL
Corossolin AGE Leaf IC50 = 3.53 × 10−1 μg/mL
Corossolone AGE Leaf IC50 = 4.80 × 10−1 μg/mL
Hexane Extract Leaf Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 77.92 ± 2.23 μg/mL Significantly reduced cell proliferation in cancer cells [31]
Ethyl acetate Extract Seed Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 = 9.3 ± 0.91 μg/mL
Methanol Extract Seed Doses: 1.56, 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL; IC50 > 100 μg/mL
Hep 2,2,15 (a Hep G2 cell line transfected with HBV) Muricin H AGE Seed IC50 = 1.18 × 10−2 μg/mL Exhibited significant activity in in vitro and cytotoxic assays in a human hepatoma cell line [81]
Muricin I AGE Leaf IC50 = 2.22 × 10−1 μg/mL
cis-Annomontacin AGE Leaf IC50 = 1.62 × 10−2 μg/mL
cis-Corossolone AGE Leaf IC50 = 4.76 × 10−2 μg/mL
Annocatalin AGE Leaf IC50 = 3.48 × 10−3 μg/mL
Annocatacin A AGE Seed IC50 = 8.17 × 10−1 μg/mL Significant in vitro cytotoxic activity [80]
Annocatacin B AGE Seed IC50 = 2.22 × 10−1 μg/mL
Muricin A AGE Seed IC50 = 5.13 × 10−3 μg/mL Cytotoxic activity [82]
Muricin B AGE Seed IC50 = 4.29 × 10−3 μg/mL
Muricin C AGE Seed IC50 = 3.87 × 10−3 μg/mL
Muricin D AGE Seed IC50 = 4.80 × 10−2 μg/mL
Muricin E AGE Seed ———
Muricin F AGE Seed IC50 = 3.86 × 10−3 μg/mL
Muricin G AGE Seed ———
Muricatetrocins A & B AGE Seed IC50 = 4.83 × 10−3 μg/mL
Longifolicin AGE Seed IC50 = 4.90 × 10−3 μg/mL
Corossolin AGE Leaf IC50 = 2.34 × 10−1 μg/mL
Corossolone AGE Leaf IC50 = 2.84 × 10−1 μg/mL
Bel-7402 (+)-(3S,6S,7R,8S)-Periconone A fungal strain Extract Seed and/or Leaf Doses: 0.01–10 μmol/mL Cytotoxic activity [38]
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide fungal strain Extract Seed
Oral cancer KB Corossolone AGE Seed ED50 = 0.1 μg/mL Toxicity against oral cancer cells in vitro [35, 83]
Corossolin AGE Seed ED50 = 0.003 μg/mL
Solamin AGE Seed ED50 = 0.3 μg/mL Toxicity against oral cancer cells in vitro [35]
Murisolin AGE Seed ED50 = 0.1 μg/mL
Annonacinone AGE Seed ED50 = 0.01 μg/mL
Annonacin AGE Leaf ED50 = 0.0001 μg/mL
Vinblastine AGE Leaf ED50 = 0.01 μg/mL
Stomach cancer C-678 Ethanol Extract Leaf IC50 < 0.22 μg/mL Cytotoxic activity [95]
Melanoma A375 H2O Extract Leaf IC50 > 500 μg/mL (24 and 72 hr) Cytotoxic activity [36]
Ethanol Extract Leaf IC50 = 20 ± 6 μg/mL (24 hr) and 20 ± 7 μg/mL (72 hr)
Pentane Extract Leaf IC50 = 140 ± 25 μg/mL (24 hr) and 120 ± 8 μg/mL (72 hr)
MDA-MB-435S n-Butanolic Extract Leaf IC50 = 29.2 μg/mL.
25, 50, 100, 200, and 400 μg/mL		 Significant cytotoxic activity [89, 90]
Skin cancer ——— 80% aqueous ethanol Extract Leaf 30 mg/kg body weight into ICR mice Suppressed tumor initiation as well as tumor promotion even at lower dosage [141]
Glioma SF-268 Ethanol (95%) Extract Seed GI50 = 8.5 μg/mL Cytotoxic activity [45]
U87MG Methanol Extract Pericarp IC50 > 80 μg/mL Cytotoxic activity [24]
Methanol Extract Leaf
Methanol Extract Seed
U87MG.ΔEGFR Methanol Extract Pericarp
Methanol Extract Leaf
Methanol Extract Leaf
Cervical cancer HeLa Ethyl acetate Extract Leaf LC50 of (2000 μg/mL) = 131.89%; and LC50 of (15.625 μg/mL) = 11.37% Induced apoptosis [37]
Ethanol-distillate water Extract Leaf LC50 of (2000 μg/mL) = 35.80%; and LC50 of (15.625 μg/mL) = 3.97%
Chloroform Extract Leaf LC50 of (2000 μg/mL) = 65.20%; and LC50 of (15.625 μg/mL) = 18.42%
n-Hexan Extract Leaf LC50 of (2000 μg/mL) = 106.53%; and LC50 of (15.625 μg/mL) = 21.41%
HEp-2 (now HeLa) Methanol Extract Leaf IC50 = 54.92 ± 1.44 μg/mL Antiproliferative and cytotoxic activities [90, 113]
Ehrlich ascite carcinoma EACC Ethanol Extract Leaf IC50 = 335.85 μg/mL Cytotoxic activity in vitro [93]
Gastric cancer BGC-823 (+)-(3S,6S,7R,8S)-Periconone A Fungal strain Extract Leaf Doses: 0.01–10 μmol/mL Cytotoxic activity [38]
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide Fungal strain Extract Leaf
Ovarian cancer A2780 (+)-(3S,6S,7R,8S)-Periconone A Fungal strain Extract Leaf
(−)-(1R,4R,6S,7S)-2-Caren-4,8-olide Fungal strain Extract Tree/Leaf
Head and neck squamous cell carcinoma (HNSC) SCC-25 H2O Extract Leaf Doses: 2.5–160 μg/mL; IC50 = 12.42 μg/mL Displayed promising cytotoxic activity and inhibition of cell proliferation via G2M cell cycle arrest [91]

ED50: median effective dose; GI50: a concentration for 50% of maximal inhibition of cell proliferation; IC25: a concentration causing 50% inhibition; IC50: a concentration causing 50% inhibition; LC50: a concentration causing 50% cell death; LD: lethal dose; MIC: minimum inhibitory concentration.