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. 2023 Jun 2;9(6):e16919. doi: 10.1016/j.heliyon.2023.e16919

Table 3.

Prospective biological targets for natural products to manage cancer.

No Source(s) Compound or extract(s) Mechanism of action(s) Experimental model(s) Key findings Refs
1 Arthrospira platensis Aqueous extract

  • •Antiproliferative

  • •Modulate apoptosis in cancer cell

  • •An in vitro study using the human Caucasian non-small-cell lung adenocarcinoma A549 cell line and human foreskin fibroblast (HFF).

  • •An in vitro study using MTT assay.

  • •Extract treatment to cancer cell lung A549 and HFF demonstrated that MDA and LDH levels in A549 cells increased significantly leading to an increase in the apoptotic process.

  • •The cell cycle decreased significantly in the G1 phase of A549 cells, indicating that the cell cycle stopped in the G1, and it prevented entering phase M. As a result, the proliferative process was decreased in the A549 cell line.

  • •In contrast, treatment with extracts showed no change in the necrosis process in both cells.

 [256]
2 Calotropis gigantea Dichloromethane extract (CGDCM) Promote apoptosis through the mitochondria-dependent pathway An in vitro study using human colorectal carcinoma HCT116 (CCL-247, ATCC, USA) and colorectal adenocarcinoma HT-29 (HTB-38, ATCC, USA).

  • •Cytotoxic effects of CGDCM on HCT116 and HT-29 cells were higher than 5-fluorouracil with IC50 of 5.9 ± 0.62 and 44.0 ± 4.06 μg/mL, respectively.

  • •Combinations of CGDCM (4, 8, and 10 μg/mL) with 5-FU (5 μM or 0.65 μg/mL) significantly enhanced the induction of apoptosis compared with either of the drugs used alone.

  • •The expression of the pro-apoptotic protein levels, such as c-caspase 3, was significantly increased in HCT116 cells treated with CGDCM and combination CGDCM with 5-FU. In contrast, the levels of anti-apoptotic (Bcl-2) and ATP were decreased.

  • •CGDCM (4 and 8 μg/mL), 5-FU (5 μM or 0.65 μg/mL), and combinations simulated the increasing ROS levels. As a result, the apoptotic process was stimulated.

 [293]
3 Bombax buonopozense Ethanol extract

  • •Antioxidant

  • •Antiproliferation

  • •An in vitro study using P815 murin lymphoblast-like mastocytoma cell line.

  • •An in vitro study using MTT assay.

  • •The extract contained flavonoids, tannins, alkaloids, and triterpenes.

  • •Ethanol extracts showed considerably potent scavenging effects on DPPH radicals with IC50 values of 10 μg/mL.

  • •Ethanol extract exhibited moderate inhibition on P815 cells in a dose above 200 μg/mL with IC50 of 74 μg/mL compared with cisplatin IC50 with IC50 of 4 μg/mL).

 [266]
4 Glycosmis parva Arborinine Inhibits the growth of tumor An in vitro study using adriamycin-resistant SGC-7901 (SGC-7901/ADR) cell line, Vincristine- resistant SGC-7901 (SGC-7901/VCR) cell line, Paclitaxel-resistant MGC803 (MGC/PTX) cell line.

  • •Arborinine exhibited a powerful inhibitory effect in SGC-7901, SGC-7901/ADR, SGC-7901/VCR, and MGC803 (MGC/PTX) with IC50 of 1.96, 0.24, 1.09, and 1.32 μM, respectively.

  • •Arborinine significantly decreased cell viability in gastric cancer cells and drug-resistant gastric cancer cells for 48 h in a dose-dependent manner.

 [46]
5 Moringa oleifera Soluble extract from leaves

  • •Induces of apoptosis

  • •Antioxidant

  • •Antiproliferative

 An in vitro study using A549 lung adenocarcinoma cells

  • •The extract exhibited considerably inhibitory effects on the proliferation of A549 lung adenocarcinoma cells in a dose/time-dependent manner.

  • •The extract exhibited potent induction of protein caspase-3 expression, stimulating apoptosis cascade.

  • •The extract decreased the level of intracellular levels in a concentration-dependent manner.

 [157]
6 Sponge Hyrtios sp. Methanol extract Induces apoptosis via activation p53 and inhibition JNK pathway An in vitro study using human colorectal carcinoma RKO (CRL-2577) and RKO-E6 (CRL-2578) cells

  • •The extract was able to induce a mitotic catastrophe

  • •The extract increased the expression of p21 protein, which correlated to increasing of p53 in RKO cells.

  • •In addition, the presence of extract suppressed JNK protein expression in RKO and RKO-E6 cells

 [126]
7 Juniperus indica Bertol The crude extract of the liquid oil Antiproliferative effect by interfering with Akt/mTOR signaling pathway An in vitro study using OECM-1 human gingival squamous cancer cells line. Induces apoptosis via activation p53 and inhibition JNK pathway [107]
8 Rhaponticum carthamoides (Willd.) Methanol extract from root Induces mitochondrial dysfunction An in vitro study using leukemia cells (K-562 and CCRF-CEM) and lung adenocarcinoma cells (A549).

  • •The extract significantly decreased viability cells in a dose-dependent manner.

  • •Mitochondrial membrane potential was disrupted and extract significantly increased mitochondrial DNA lesions in ND1 and ND5 genes and DNA damage in the TP53 gene.

 [245]
9 Xanthium strumarium Chloroform and methanol extracts from fruit Inhibit autophagy-related (ATG) proteins An in vitro study using ATG4B cleavage assays.

  • •Extracts significantly suppressed the cell invasion, migration, and live cells in colorectal cancer cells.

  • •The presence of extracts significantly inhibited cell migration.

  • •The extracts decreased viability cells in a dose-dependent manner.

  • •Extracts increased luciferase activity compared with cells without treatment, indicating that autophagy in cancer cells was suppressed.

  • •The levels of MAP1LC3-II protein were increased, indicating that extracts inhibited autophagy proteolytic activity.

 [39]
10 Litchi chinensisSonnnerat n-butyl alcohol extract of Litchi seed (NLS)

  • •Induces cell apoptosis by inhibiting Akt/GSK-3β signaling pathway and activating the intrinsic apoptotic pathway

  • •Inhibits cell migration

 An in vitro study using prostate cancer cell lines PC3, DU145, RM1, and C4–2B

  • •NLS considerably inhibited the growth and proliferation of prostate cancer cells in a concentration-dependent manner.

  • •NLS activated the intrinsic apoptotic pathway by inducing the cleaved caspase-9 in cells and cleaved Caspase-7.

  • •NLS suppressed the expression of anti-apoptotic Bcl2 and increased pro-apoptotic protein Bax in both PC3 and DU145 cells.

  • •NLS significantly inhibited the phosphorylation of Akt and GSK-3β in both PC3 and DU145 cell lines.

  • •NLS promoted cell cycle arrest at the G1/S phase through suppression of cyclin-dependent kinases (Cdks) and upregulation of CDK inhibitor

 [88]
11 Annona muricata L. Ethanol extract from leaves

  • •Induces cell apoptosis

  • •Decreases cell viability

 An in vitro study using liver cancer HepG2 cells and colon cancer HCT116 cells

  • •The extract significantly decreased cell viability in both HepG2 and HCT116 cells in a concentration-dependent manner.

  • •The extract remarkably upregulated the expression of HSP70, GRP94, DPI-related protein 5, Bip, CHOP, and phosphorylation of PERK and eIF2α in the cancer cell line.

 [160]
12 Neptunia oleracea Lour (water mimosa) Methanol extract

  • •Induces cell apoptosis

  • •Antiproliferation

 An in vitro study using jurkat (acute T cell leukemia) and MV-4-11(biphenotypic B myelomonocytic leukemia) cell line.

  • •The extract significantly induced apoptosis in cancer cells by suppressing Bcl-2, c-Myc, and pERK1/2 protein levels. In contrast, cleaved PARP was increased.

 [27]
13 Cyanthillium cinereum (L.) Sesquiterpene lactones

  • •Cytotoxicity activity

  • •Inhibit DNA replication by inducing S-phase arrest

  • •Induce cell apoptosis

 An in vitro study in 786-O cell line, K-562 leukemic cell line, and MCF-7 breast cancer cell line

  • •Compound 1 at 12.5 and 25.0 μg/mL concentrations significantly induced S phase arrest with IC50 of 12.02 and 13.3%, respectively, compared to the control cell.

  • •Compound 1 increased ROS production in 786-O cells in a time-dependent manner but gradually was weaker after incubation for 2 h.

  • •Compound 1 significantly increased LDH release in a time/concentration-dependent manner.

 [60]
14 Tourneuxia variifolia Ethyl acetate (EtOAc) and n-butanol (n- BuOH) extracts Inhibit the activity of HeLa cells An in vitro study using human cervical adenocarcinoma (HeLa) cell line

  • •EtOAc and n-BuOH extracts contained high quantities of phenolic compounds.

  • •The EtOAc extract showed potent anticancer activity with IC50 of 46.797 ± 0.060 mg/mL.

 [309]
15 Tapinanthus sp. (Loranthaceae)

  • •Methanol extract from leaves

  • •Flavonoid glycoside (compound 3)

 Inhibit proliferation An in vitro study using glioblastoma (U87MG, C6) and prostate (PC-3) cancer cells

  • •The methanol leaves extract exhibited great anticancer activity in U87 with IC50 of 21.40 mg/mL and PC-3 cells with IC50 of 10.26 mg/mL.

  • •Compound 3, the most potent, inhibits the proliferation of C6 and PC-3 cells with IC50 of 38.84 and 21.33 mM, respectively.

 [81]
16 Xylocarpus granatum Ethyl acetate extract from leaves

  • •Antioxidant

  • •Inhibits the activity of cancer cells

 An in vitro study using HeLa, T47D, and HT-29 cell line

  • •Antioxidant activity was examined using DPPH assay, and the extract showed intermediate antioxidant activity with IC50 of 84.93 ± 12.93 ppm.

  • •Cytotoxicity of extract in HeLa, T47D, and HT29 was determined using MTT assay and exhibited IC50 of 42.50 ± 36.56, 559.57 ± 857.79, 77.76 ± 66.70 ppm, respectively.

  • •Fraction 5 of the extract revealed the most potent inhibition against HT-29 with IC50 of 23.12 ppm.

 [53]
17 Diospyros kaki L. Total flavonoids from persimmon leaves (FPL)

  • •Inhibit proliferation and migration of cell

  • •Induce cell apoptosis by activation of oxidative stress and mitochondrial-related apoptotic.

 An in vitro study in prostate cancer PC-3 cells

  • •FPL induced a cytotoxic effect in a concentration-dependent manner starting at 12.5–100 μg/ml.

  • •FPL-induced cell apoptosis was marked by increased ROS, MDA, nitrite, iNOS activity, and mitochondrial membrane permeability.

  • •FPL significantly suppressed protein Bcl-2, increased BAX and cleaved caspase-3, and released cytochrome c.

  • •FPL significantly inhibited the migration of PC-3 cells.

 [62]
18 Tephroseris kirilowii (Turcz.) Holub. Isorhamnetin (IH), genkwanin (GN), acacetin (Aca)

  • Induce apoptosis by reducing PI3Kγ -p100 mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway.

  • •An in vitro study using human breast cancer cells (MDA-MB-231)

  • •In-silico using Surflex-Dock in SYBYL2.0

  • •IH, GN, and Aca inhibited cell proliferation in a concentration-dependent manner associated with cell cycle arrest at the G2/M phase.

  • •IH, GN, and Aca induced cell apoptosis due to decreased Bcl-2 and Bcl-xL and increased levels of p53.

  • •IH, GN, and Aca inhibit expression of PI3K/AKT/mTOR/p70S6K/ULK1, as well as PI3Kγ.

  • •IH, GN, and Aca-induced autophagic correlated with decreasing of p62 and increasing in levels of ATG5.

  • •The docking results demonstrated that IH, GN, and Aca are able to bind to the specific functional catalytic amino acids of PI3Kγ with hydrophobic interaction, such as LYS-833 and ASP-964.

 [310]
19 Artemisia aucheri Boiss. Methanol extract from leaves

  • •Cytotoxicity

  • •Induces apoptosis

  • •Inhibits migration cell

 An in vitro study using HT29 colon cancer cells

  • •The cytotoxicity effect of the extract was dose-dependent. The higher concentration showed lower cell viability.

  • •The level of malondialdehyde was significantly increased in the treated cells with the extract.

  • •The extract significantly induced apoptosis and inhibited the migration of cells.

 [6]
20 Calligonum comosum (L’Her) Methanol fruit hairs extract (MFH)

  • •Antiproliferation

  • •Induces apoptosis

 An in vitro study using human hepatocarcinoma cells (HepG2)

  • •MFH exerted potent antiproliferation activity with IC50 of 10.4 mg/ml.

  • •MFH induced overexpression of mRNA transcript levels of gen p53, caspase-3, and Bax as pro-apoptotic. In contrast, the level of Bcl-2, an anti-apoptotic marker gene, was suppressed.

 [9]
21 Bombax buonopozense Ethanol extract from stem bark

  • •Antiproliferation

  • •Antioxidant

  • •An in vitro study in P815 murin lymphoblast-like mastocytoma cell line using the MTT assay

  • •Antioxidant activity was measured by the 2,2’-diphenyl-1- picrylhydrazyl (DPPH) free radical assay

  • •The extract showed moderate inhibitory activity against P815 in a dose-dependent manner in which IC50 above 200 μg/mL was 74 μg/mL.

  • •The antioxidant activity revealed IC50 of 10 μg/mL at a concentration of 220 μg/mL.

 [266]
22 Raphanus sativus L. Ethanol extract from seed

  • •Inhibits proliferation and cell migration mediated by the β-catenin signaling pathway

  • •Induces apoptosis

 An in vitro study using oral squamous cell carcinoma (KB and KBCD133+)

  • •The extract decreased β-catenin activity, expression, and nuclear translocation in a dose-dependent manner.

  • •The extract could induce apoptosis by upregulating PARP, Bax, and downregulating Bcl-2.

  • •In addition, the p-GSK-3b level and p-GSK-3b/t-GSK-3b ratio were significantly decreased dose-dependently, leading to induced apoptosis.

 [3]
23 Orobanche crenata Methanol extract

  • •Antioxidant

  • •Cytotoxic

  • •Induces apoptosis

 An in vitro study using hepatocellular carcinoma (HepG2), human prostate cancer (PC3), human breast adenocarcinoma (MCF-7), and human colon carcinoma (HCT-116)

  • •The extract exhibited potent antioxidant activity.

  • •The extract revealed a remarkable cytotoxic effect on HepG2, PC3, MCF-7, and HCT-116 cells with IC50 values of 30.3, 111, 89.6, and 28.6 mg/mL, respectively.

  • •The presence of extract in a concentration-dependent manner increased LDH release, leading to membrane cell damage in HCT-116 cells.

  • •Extract activated caspase-3 activity in HCT-116 cells to induce cell apoptosis.

 [96]