MDA-MB-435 breast cancer cells, downregulation of oncogenic miR-155 was
observed after treatment with genistein which led to the expression FOXO3, PTEN,
casein kinase, and p27. Interestingly, the inhibition of invasiveness and metastasis
were achieved as miR-155 has been demonstrated to escalate in various tumours
(De La Parra et al. 2016). When oncogenic miR-23b-3p was reduced in renal cancer
cells treated with genistein, expression of target PTEN begin to enhance followed
by reduced expression of cancer-related genes PI3K (phosphatidylinositol-3kinase), Akt and IL-32 (interleukin-32) (Zaman et al. 2012). Genistein increased the
levels of miR-145 in retinoblastoma cell (Y79) cell, thereby inhibiting ABCE1
target gene to demonstrate anti-proliferation and growth impediment. The gene
ABCE1 is known as a member of ATP-binding cassette (ABC) transporters which
carries the responsibility for actively transferring molecules across phospholipid
bilayers (Wei et al. 2017). Genistein exhibited apoptotic in laryngeal cancer when
the expression of miR-1469 was greatly up-regulated followed by a suppression in
myeloid cell leukemia 1, an anti-apoptotic member of Bcl-2 family (Ma et al. 2018).
In the case of pancreatic cancer cells, it was reported that following treatment with
genistein, the expression of miR-223 was significantly decreased. Further investigation also indicated the up-surge of F-box/WD repeat-containing protein 7 gene, a
tumour suppressor gene which was one of the targets of miR-223 (Ma et al. 2013).
The expression of miR-29b in U266 multiple myeloma cells were revealed with the
administration of genistein. The miR-29b observes a significant twofold increase
that targets the NF-jB expression, hence promoting and restoring apoptosis in
U266 multiple myeloma cells (Xie et al. 2016).
Indole-3-carbinol (I3C) is a constituent of cruciferous vegetables that has the
prospecting value as a chemo-preventive agent (Beier 1990) according to many
studies (Chinni and Sarkar 2002; Rahman et al. 2004). It mainly works by modifying
estrogen metabolism upon consumption to aid its cancer-preventive measurements.
Concurrent researches have provided substantiate evidence indicating I3C in cell
growth arrest, cell proliferation prevention and apoptosis (Takada et al. 2005; Weng
et al. 2007; Omar et al. 2009). In human breast cancer cells (MCF-7), I3C has
demonstrated an upregulation of miR-34a (Hargraves et al. 2016). The higher
expression of miR-34a targets Bcl-2 and other anti-apoptotic proteins hinders chromatin silencers of p53 genes and assist the repression of CDK4, CDK6, and cyclin D1
(He et al. 2007; Hermeking, 2010). Taken together, the expression of miR-34a
modulates p53 tumour suppressor escalation and its downstream gene 21 to achieve
apoptosis (He et al. 2007). In an in vivo lung cancer study, female mice were observed
after exposing to vinyl carbamate (VC). A plethora of miRNAs were down-regulated
which includes miR-21, miR-31, miR-130a, miR-146b, and miR-377 where reversed
changes were observed in mice treated with carcinogen only. Further analysis of
miR-21 indicated PTEN, PDCD4, and reversion-inducing-cystein-rich protein with
Kazal motifs as potential targets for the oncogenic effect of miR-21 and the
chemopreventive activity of I3C (Melkamu et al. 2010). Identically, in hepatocellular
carcinoma (HCC) cell, I3C was also revealed to reduce and prevent the progression of
tumorigenicity by arresting miR-21 (Wang et al. 2015).
142
B. Cilwyn et al.
observed after treatment with genistein which led to the expression FOXO3, PTEN,
casein kinase, and p27. Interestingly, the inhibition of invasiveness and metastasis
were achieved as miR-155 has been demonstrated to escalate in various tumours
(De La Parra et al. 2016). When oncogenic miR-23b-3p was reduced in renal cancer
cells treated with genistein, expression of target PTEN begin to enhance followed
by reduced expression of cancer-related genes PI3K (phosphatidylinositol-3kinase), Akt and IL-32 (interleukin-32) (Zaman et al. 2012). Genistein increased the
levels of miR-145 in retinoblastoma cell (Y79) cell, thereby inhibiting ABCE1
target gene to demonstrate anti-proliferation and growth impediment. The gene
ABCE1 is known as a member of ATP-binding cassette (ABC) transporters which
carries the responsibility for actively transferring molecules across phospholipid
bilayers (Wei et al. 2017). Genistein exhibited apoptotic in laryngeal cancer when
the expression of miR-1469 was greatly up-regulated followed by a suppression in
myeloid cell leukemia 1, an anti-apoptotic member of Bcl-2 family (Ma et al. 2018).
In the case of pancreatic cancer cells, it was reported that following treatment with
genistein, the expression of miR-223 was significantly decreased. Further investigation also indicated the up-surge of F-box/WD repeat-containing protein 7 gene, a
tumour suppressor gene which was one of the targets of miR-223 (Ma et al. 2013).
The expression of miR-29b in U266 multiple myeloma cells were revealed with the
administration of genistein. The miR-29b observes a significant twofold increase
that targets the NF-jB expression, hence promoting and restoring apoptosis in
U266 multiple myeloma cells (Xie et al. 2016).
Indole-3-carbinol (I3C) is a constituent of cruciferous vegetables that has the
prospecting value as a chemo-preventive agent (Beier 1990) according to many
studies (Chinni and Sarkar 2002; Rahman et al. 2004). It mainly works by modifying
estrogen metabolism upon consumption to aid its cancer-preventive measurements.
Concurrent researches have provided substantiate evidence indicating I3C in cell
growth arrest, cell proliferation prevention and apoptosis (Takada et al. 2005; Weng
et al. 2007; Omar et al. 2009). In human breast cancer cells (MCF-7), I3C has
demonstrated an upregulation of miR-34a (Hargraves et al. 2016). The higher
expression of miR-34a targets Bcl-2 and other anti-apoptotic proteins hinders chromatin silencers of p53 genes and assist the repression of CDK4, CDK6, and cyclin D1
(He et al. 2007; Hermeking, 2010). Taken together, the expression of miR-34a
modulates p53 tumour suppressor escalation and its downstream gene 21 to achieve
apoptosis (He et al. 2007). In an in vivo lung cancer study, female mice were observed
after exposing to vinyl carbamate (VC). A plethora of miRNAs were down-regulated
which includes miR-21, miR-31, miR-130a, miR-146b, and miR-377 where reversed
changes were observed in mice treated with carcinogen only. Further analysis of
miR-21 indicated PTEN, PDCD4, and reversion-inducing-cystein-rich protein with
Kazal motifs as potential targets for the oncogenic effect of miR-21 and the
chemopreventive activity of I3C (Melkamu et al. 2010). Identically, in hepatocellular
carcinoma (HCC) cell, I3C was also revealed to reduce and prevent the progression of
tumorigenicity by arresting miR-21 (Wang et al. 2015).
142
B. Cilwyn et al.