160
concentration) induced apoptosis, inhibited cell growth and attachment, fragmented
chromatin and also blocked the sub-G1 phase of the cell cycle. In vivo studies in
mice as animal model of breast cancer, showed an inhibition of tumour progression
and increased apoptosis (Delphi and Sepehri 2016). Moreover, pectin modified with
heat, enzymes, and chemicals possesses better antitumor activity than the native or
unmodified pectin. Modified pectins induce programmed cell death by the detachment of cells from its matrix i.e. ‘anoikis’ (Jackson et al. 2007). Heat modified citrus pectin has been reported to possess apoptotic action over prostate cancer cells
(Jackson et al. 2007). Leclere et al. (2015) revealed cell death inducing activity in
HepG2 and A549 cells of heat modified citrus pectin. The mechanism involved
caspase 3 cleavage which is different from the classical apoptosis. Further research
revealed that the cytotoxic activity is related to molecules with molecular weight
corresponding to oligogalacturonic acid with lower degree of polymerization. Heat
modification of galacturonic acid generates active molecules for instance, 4,5- dihy
droxy- 2-cyclopenten-1-one (cytotoxic molecule) from polygalacturonc acid through
Maillard reactions. This molecule forms covalent adducts on cysteines, leading to
protein denaturation and ubiquitination. Protein degradation brought by tubulin
adducts results in prevention of mitosis. Ubiquitinylation of proteins inhibits proteosome, causing the activation of caspase 8 and hence apoptosis. Pectin obtained
by the enzymatic hydrolysis of Glinus opposite folius showed better immune modulating effects than the native forms (Inngjerdingen et al. 2007). pH modified citrus
pectin revealed an inhibitory action on tumor growth, metastases, and angiogenesis
(Glinsky and Raz 2009). pH modified pectin increases solubility due to β-elimination
causing a significant reduction in the DE and reduces the pectin chain length. Due
to acid-hydrolysis and β-elimination certain domains in pectin molecule get enriched
that are regarded as its pharmacophores (i.e. structures required for interaction with
a biological target to trigger response). These pharmacophores are present in the
RG-I domain and are mainly galactans rich in β-galactosides. Gal-3 (Galectin-3), a
key target in metastasis recognizes these pharmacophores via a carbohydrate recognition domain. Gal-3 is a lectin that has been reported to show over-expression in
metastatic cancers promoting cell migration and survival (Fortuna-Costa et al.
2014). Modified pectins that are rich in RG-I domains present β-galactosides to the
carbohydrate recognition domain of Gal-3 efficiently, as they are comprise more of
galactosides overxylanan and arabinan residues, which do not resist acid-hydrolysis
effectively compared to galactans. When pro-metastatic Gal-3 gets binded, this
blocks its interaction to other proteins and peptides, thereby arresting all possible
pathways involving cell adhesion, migration and apoptosis. Cheng et al. (2013)
reported considerable anti-tumor activity in okra and potato pectins, rich in
RG-Idomains. Maxwell et al. (2016) studied apoptosis inducing activity of colon
cancer cells in modified sugar beet pectin. Sugar beet pectin was found to be about
7 times rich in RG-I domains compared to citrus pectin. Pectin treated with alkali
exhibited an increased ratio of RG-I to HG and also showed an enhancement in
cancer cell apoptosis. Further insights into the mechanisms involving pectin could
help in the treatment of cancers.
N. Noor et al.
concentration) induced apoptosis, inhibited cell growth and attachment, fragmented
chromatin and also blocked the sub-G1 phase of the cell cycle. In vivo studies in
mice as animal model of breast cancer, showed an inhibition of tumour progression
and increased apoptosis (Delphi and Sepehri 2016). Moreover, pectin modified with
heat, enzymes, and chemicals possesses better antitumor activity than the native or
unmodified pectin. Modified pectins induce programmed cell death by the detachment of cells from its matrix i.e. ‘anoikis’ (Jackson et al. 2007). Heat modified citrus pectin has been reported to possess apoptotic action over prostate cancer cells
(Jackson et al. 2007). Leclere et al. (2015) revealed cell death inducing activity in
HepG2 and A549 cells of heat modified citrus pectin. The mechanism involved
caspase 3 cleavage which is different from the classical apoptosis. Further research
revealed that the cytotoxic activity is related to molecules with molecular weight
corresponding to oligogalacturonic acid with lower degree of polymerization. Heat
modification of galacturonic acid generates active molecules for instance, 4,5- dihy
droxy- 2-cyclopenten-1-one (cytotoxic molecule) from polygalacturonc acid through
Maillard reactions. This molecule forms covalent adducts on cysteines, leading to
protein denaturation and ubiquitination. Protein degradation brought by tubulin
adducts results in prevention of mitosis. Ubiquitinylation of proteins inhibits proteosome, causing the activation of caspase 8 and hence apoptosis. Pectin obtained
by the enzymatic hydrolysis of Glinus opposite folius showed better immune modulating effects than the native forms (Inngjerdingen et al. 2007). pH modified citrus
pectin revealed an inhibitory action on tumor growth, metastases, and angiogenesis
(Glinsky and Raz 2009). pH modified pectin increases solubility due to β-elimination
causing a significant reduction in the DE and reduces the pectin chain length. Due
to acid-hydrolysis and β-elimination certain domains in pectin molecule get enriched
that are regarded as its pharmacophores (i.e. structures required for interaction with
a biological target to trigger response). These pharmacophores are present in the
RG-I domain and are mainly galactans rich in β-galactosides. Gal-3 (Galectin-3), a
key target in metastasis recognizes these pharmacophores via a carbohydrate recognition domain. Gal-3 is a lectin that has been reported to show over-expression in
metastatic cancers promoting cell migration and survival (Fortuna-Costa et al.
2014). Modified pectins that are rich in RG-I domains present β-galactosides to the
carbohydrate recognition domain of Gal-3 efficiently, as they are comprise more of
galactosides overxylanan and arabinan residues, which do not resist acid-hydrolysis
effectively compared to galactans. When pro-metastatic Gal-3 gets binded, this
blocks its interaction to other proteins and peptides, thereby arresting all possible
pathways involving cell adhesion, migration and apoptosis. Cheng et al. (2013)
reported considerable anti-tumor activity in okra and potato pectins, rich in
RG-Idomains. Maxwell et al. (2016) studied apoptosis inducing activity of colon
cancer cells in modified sugar beet pectin. Sugar beet pectin was found to be about
7 times rich in RG-I domains compared to citrus pectin. Pectin treated with alkali
exhibited an increased ratio of RG-I to HG and also showed an enhancement in
cancer cell apoptosis. Further insights into the mechanisms involving pectin could
help in the treatment of cancers.
N. Noor et al.