Table 3.
A Summary of in vitro and in vivo Studies of M. indica Extracts and Their Phytochemicals Evaluated for Anti-Breast Cancer Potentials
| Extracts/Phytochemicals | Cell Lines/Animals (Sex) | Observations | Mechanism of Action | References |
|---|---|---|---|---|
| Bark | MDA-MB-231 cell line | ↓ Cell proliferation | Inhibition of NFκB signalling pathway | García-Rivera et al (2011)34 |
| Kernel | MCF-7 cell line MDA-MB-231 cell line |
↓ Cell viability | N/A | Abdullah et al (2014)39 |
| MCF-7 cell line | ↑ ROS and MDA levels ↓ GSH level ↑ p53 level ↑ Pro-apoptotic markers (Bax and cytochrome c) ↓ Pro-survival markers (Bcl-2) ↑ Caspases 7, 8 and 9 activities |
Activation of oxidative stress-induced cell death | Abdullah et al (2015a)160 | |
| MDA-MB-231 cell line | ↑ ROS and MDA levels ↓ GSH level ↑ p53 level ↑ Pro-apoptotic markers (Bax and cytochrome c) ↓ Pro-survival markers (Bcl-2) ↑ Caspases 3, 8 and 9 activities |
Activation of oxidative stress-induced cell death | Abdullah et al (2015b)161 | |
| Leaves | BT-474 cell line | ↓ Cell viability | N/A | Ganogpichayagrai et al (2017)50 |
| MCF-7 cell line MDA-MB-231 cell line |
↓ Cell viability | Antioxidant activity | Fernández-Ponce et al (2017)27 | |
| Pulp | MCF-7 cell line | ↓ Cell proliferation | Antioxidant activity | García-Solís et al (2009)25 |
| BT-474 cell line Mice bearing BT-474 xenografts (female) |
↓ Cell proliferation ↓ Tumor volume |
Suppression of PI3K/AKT pathway Induction of miR-126 expression |
Banerjee et al (2015)24 | |
| Peel and pulp | MCF-7 cell line | ↓ Cell viability | Modulation of PPARs | Wilkinson et al (2011)26 |
| MCF-7 cell line MDA-MB-231 cell line |
↓ Cell viability (peel extract only) ↑ Cell death (peel extract only) |
N/A | Hoang et al (2015)52 | |
| MCF-7 cell line | ↓ Cell viability (peel extract only) | Modulation of intracellular Ca2+ signalling | Taing et al (2015)53 | |
| Peel | MCF-7 cell line | ↓ Cell viability | Antioxidant activity Inhibition of aromatase enzymatic activity and expression |
Shaban et al (2016)51 |
| Polyphenols | MDA-MB-231 cell line | ↓ Cell growth | Antioxidant activity | Noratto et al (2010)55 |
| MCF10DCIS cell line | ↓ Cell proliferation | Suppression of PI3K/AKT pathway | Nemec et al (2016)56 | |
| Mice bearing MCF10DCIS xenografts (female) | ↓ Tumor volume | Suppression of PI3K/AKT pathway Activation of AMPK signalling pathway |
Nemec et al (2017)57 | |
| Mangiferin | MCF-7 cell line T47D cell line MDA-MB-231 cell line BT-549 cell line Mice bearing MDA-MB-231 xenografts (female) |
↓ Cell proliferation ↑ Apoptosis ↓ Cell migration ↓ Cell invasion ↓ Tumor volume ↓ Tumor weight |
Inactivation of β-catenin pathway | Li et al (2013)66 |
| MCF-7 cell line MDA-MB-231 cell line |
↓ Cell viability ↓ Cell migration ↓ Cell invasion |
Inhibition of Rac1/WAVE2 signalling pathway | Deng et al (2018)67 | |
| MCF-7 cell line | ↓ Cell viability ↓ Proliferation marker (PCNA) ↓ Pro-survival markers (Bcl-2) ↑ Pro-apoptotic markers (Bax, caspase 9 and p27) ↓ Cell migration |
Inhibition of HMG-CoA reductase, proteasome and plasmin enzymatic activities | Cuccioloni et al (2016)68 | |
| MCF-7 cell line | ↓ Cell viability | N/A | Louisa et al (2014)74 | |
| MDA-MB-231 cell line | ↔ Cell viability | Inhibition of NFκB signalling pathway | García-Rivera et al (2011)34 | |
| MCF-7 cell line | ↔ Cell viability | Modulation of ER activity | Wilkinson et al (2015)75 | |
| MCF-7 cell line | N/A | Inhibition of NFκB signalling pathway | Sarkar et al (2004)228 | |
| Norathyriol | MCF-7 cell line | ↓ Cell viability | Modulation of ER activity | Wilkinson et al (2015)75 |
| Gallotannin (5GG) | MCF-7 cell line | ↓ Cell growth | Suppression of PI3K/AKT pathway Modulation of ER activity |
Hua et al (2006)94 |
| MCF-7 cell line | ↓ Cell growth ↑ G1-phase arrest |
Modulation of cell cycle regulators | Chen et al (2003)95 | |
| Gallic acid | MDA-MB-231 cell line | ↓ Cell viability | Inhibition of NFκB signalling pathway | García-Rivera et al (2011)34 |
| MCF-7 cell line | ↓ Cell proliferation ↑ S-phase and G2/M-phase arrest |
Modulation of cell cycle regulators | Hsu et al (2011)111 | |
| MCF10DCIS cell line | ↓ Cell proliferation | N/A | Nemec et al (2016)56 | |
| MCF-7 cell line | ↓ Cell growth ↑ Apoptosis ↑ Fas, FasL levels and caspase 8 activity ↓ ΔΨm ↑ Bax/Bcl-2 ratio, cytochrome c level and caspase 9 activity ↑ Caspase 8-mediated Bid cleavage |
N/A | Ke Wang et al (2014)112 | |
| Pyrogallol | MCF10DCIS cell line | ↓ Cell proliferation | Suppression of PI3K/AKT pathway | Nemec et al (2016)56 |
| Mice bearing MCF10DCIS xenografts (female) | ↓ Tumor volume | Suppression of PI3K/AKT pathway Activation of AMPK signalling pathway |
Nemec et al (2017)57 | |
| Methyl gallate | MCF10DCIS cell line | ↓ Cell proliferation | N/A | Nemec et al (2016)56 |
| Quercetin | MCF-7 cell line | ↓ Cell viability | Modulation of ER activity | Wilkinson et al (2015)75 |
| MCF-7 cell line | ↓ Cell growth ↑ Apoptosis ↑ S-phase arrest |
Activation of oxidative stress-induced cell death | Zhang et al (2012)147 | |
| MCF-7 cell line | ↓ Cell viability ↑ Apoptosis ↑ S-phase arrest ↑ ATF6, GRP78, PERK and GADD153 levels ↓ ΔΨm ↑ AIF, Bid, caspase 6, caspase 8, caspase 9, Fas and TRAIL levels ↓ Bcl-2, PARP and XIAP levels ↑ Caspases 6, 8 and 9 activities ↑ AIF and GADD153 nuclear translocation |
Modulation of intracellular Ca2+ signalling Modulation of cell cycle regulators |
Chou et al (2010)148 | |
| MDA-MB-231 cell line | ↓ Cell viability ↑ Apoptosis ↑ G2/M-phase arrest ↑ ATF6-α, GRP78 and PERK levels ↓ Pro-caspase 3 ↓ ΔΨm ↑ Bax, caspase 3, caspase 8, cytochrome c and Fas levels ↓ PARP and XIAP levels ↑ Caspases 3, 8 and 9 activities ↑ AIF level and mitochondrio-nuclear translocation |
Modulation of intracellular Ca2+ signalling Modulation of cell cycle regulators |
Chien et al (2009)149 | |
| MDA-MB-231 cell line Mice bearing MDA-MB-231 xenografts (female) |
↓ Cell proliferation ↑ Apoptosis ↑ G2/M-phase arrest ↑ Caspases 3 and 7 activities ↓ Cell migration ↓ Tumor growth |
Suppression of PI3K/AKT pathway Activation of AMPK signalling pathway |
Rivera Rivera et al (2016)150 |
Notes: ↑ increased; ↓ decreased; ↔ no significant change.
Abbreviations: AIF, apoptosis-inducing factor; AMPK, AMP-activated protein kinase; ATF6-α, AMP-dependent transcription factor 6-alpha; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; Bid, BH3-interacting domain death agonist; Ca2+, calcium; ER, estrogen receptor; Fas, Fas cell surface death receptor; FasL, Fas ligand; GADD153, growth arrest and DNA damage 153; GRP78, 78-kDa glucose-regulated protein; GSH, glutathione; HMG-CoA reductase, 3-hydroxy-3-methyl-glutaryl-coenzyme A; MDA, malondialdehyde; miR-126, microRNA-126; ΔΨm, mitochondrial membrane potential; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; PARP, Poly-ADP ribose polymerase; PCNA, proliferating cell nuclear antigen; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PI3K/AKT, phosphoinositide 3-kinase/protein kinase B; PPARs, peroxisome proliferator-activated receptors; ROS, reactive oxygen species; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; XIAP, X-linked inhibitor of apoptosis protein; 5GG, pentagalloylglucose.