128 Marine Macro- and Microalgae: An Overview
apoptosis dependent on regulatory cascades involved in the activation of caspase-3 (Ale et al. 2011).
Polysaccharides from the algae Sargassum latifolium showed selective cytotoxicity against lymphoblastic
leukaemia (1301 cells), leading to a major disturbance of the cell cycle, including arrest in S-phase and
apoptotic (rather than necrotic) induced-cell death (Gamal-Eldeen et al. 2009).
Polyunsaturated fatty acids (PUFA) have also been shown to possess anti-proliferative potential.
Chiu et al. (2004) investigated whether docosahexaenoic acid (DHA) from the cultured microalga
Crypthecodinium cohnii was able to inhibit growth of human breast carcinoma MCF-7 cells. Indeed,
DHA produced a dose-dependent growth inhibition of breast cancer cells upon a 72-h incubation with
40–160 µM of the fatty acid. DNA flow cytometry showed that DHA induced sub-G1 cells, or apoptotic
cells, by 64.4% to 171.3% of control levels upon incubations with 80 µM of the fatty acid. Western
blot studies further suggested that DHA did not modulate the expression of pro-apoptotic Bax protein
but induced a time-dependent downregulation of anti-apoptotic Bcl-2 expression. Therefore, Chiu et al.
(2004) suggested that DHA from the cultured Crypthecodinium cohnii is effective in controlling cancer
cell growth and in inducing apoptosis by downregulation of Bcl-2.
Carotenoids are well known antioxidant molecules that may display a strong anti-proliferative
effect. Cha et al. (2008) isolated carotenoids from the marine microalga Chlorella ellipsoidea displaying
antiproliferative activity. Partially purified extracts of C. ellipsoidea inhibited HCT116 cell growth in
a dose-dependent manner, yielding IC 50 values of 40.73 µg/mL. In addition, treatment with Chlorella
extracts enhanced the fluorescence intensity typical of early apoptotic cell population in HCT-116 cells.
Astaxanthin, a red carotenoid accumulated by Haematoccocus pluvialis cysts, showed a potent antitumoural activity against oral and colon cancers. A few Dunaliella species also accumulate considerable
amounts of isoforms of β-carotene, which displayed a strong anti-proliferative effect against MCF-7 cell
line, along with astaxanthin (Guedes et al. 2011).
Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis, and
angiogenesis. Matrix metalloproteinases (MMP) are a family of zinc-dependent neutral endopeptidases
collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMP
can be detected in tumour tissue or in the serum of patients with advanced cancer and their role as
prognostic indicators in cancer has been assessed. Also, MMP inhibitors are in clinical trials with
cancer patients (Vihinen and Kähäri 2002). 6,6’-bieckol is a phloroglucinol derivative isolated from
the marine alga Ecklonia cava that inhibited MMP-2 and -9 gene expression by down-regulation of
NF-κB. Furthermore, 6,6’-bieckol suppressed the migration of HT1080 cell line (Zhang et al. 2010).
An Ecklonia cava phloroglucinol derivative, dioxinodehydroeckol, not only inhibited the proliferation
of human breast cancer cells (Kong et al. 2009), but also exerted a higher anti-proliferative activity
in MCF-7 human cancer cells as well as apoptosis induction in a dose-dependent manner. Treatment
with dioxinodehydroeckol induced caspase-3 and -9 activities, DNA repair enzyme poly-(ADP-ribose)
polymerase (PARP) cleavage, and pro-apoptotic (p53 and Bax) gene expression. It also led to a downregulation in Bcl-2 anti-apoptotic gene. In addition, the NF-κB family and NF-κB-dependent activated
genes were down-regulated (Kong et al. 2009). Apart from the inflammatory response, the inducible
transcription factor NF-κB plays an important role in the regulation of carcinogenic responses. Although
normal, NF-κB activation is necessary for cell survival and immunity, deregulated NF-κB expression is
common in cancer development (Folmer et al. 2008).
Prenylated bromohydroquinones are cymopol-related metabolites that are known to accumulate
in the marine chlorophyte Cymopolia barbata. One of these compounds, 7-hydroxycymopolone,
was investigated for cytotoxicity against three cancerous cell lines and one non-tumoural cell line.
7-hydroxycymopolone selectively impacted the viability of HT29 colon cancer cells (IC 50 = 19.82
μM) with similar potency to the known chemotherapeutic drug, fluorouracil (IC 50 = 23.50 μM). In
comparison, the effect on non-tumoural colon cells resulted in an IC 50 value of 55.65 and 55.51 μM
for 7-hydroxycymopolone and fluorouracil, respectively (Badal et al. 2012). The endemic New Zealand
brown alga Perithalia capillaris afforded a bis-prenylated quinone through bioactivity-directed isolation
that was potent at inhibiting the proliferation of HL60 cells (IC 50 0.34 µM; Sansom et al. 2007).
Fucosterol, identified as the most abundant phytosterol from the hexane fraction of Sargassum
angustifolium, was considered to be responsible for the cytotoxic effect of this extract against human
apoptosis dependent on regulatory cascades involved in the activation of caspase-3 (Ale et al. 2011).
Polysaccharides from the algae Sargassum latifolium showed selective cytotoxicity against lymphoblastic
leukaemia (1301 cells), leading to a major disturbance of the cell cycle, including arrest in S-phase and
apoptotic (rather than necrotic) induced-cell death (Gamal-Eldeen et al. 2009).
Polyunsaturated fatty acids (PUFA) have also been shown to possess anti-proliferative potential.
Chiu et al. (2004) investigated whether docosahexaenoic acid (DHA) from the cultured microalga
Crypthecodinium cohnii was able to inhibit growth of human breast carcinoma MCF-7 cells. Indeed,
DHA produced a dose-dependent growth inhibition of breast cancer cells upon a 72-h incubation with
40–160 µM of the fatty acid. DNA flow cytometry showed that DHA induced sub-G1 cells, or apoptotic
cells, by 64.4% to 171.3% of control levels upon incubations with 80 µM of the fatty acid. Western
blot studies further suggested that DHA did not modulate the expression of pro-apoptotic Bax protein
but induced a time-dependent downregulation of anti-apoptotic Bcl-2 expression. Therefore, Chiu et al.
(2004) suggested that DHA from the cultured Crypthecodinium cohnii is effective in controlling cancer
cell growth and in inducing apoptosis by downregulation of Bcl-2.
Carotenoids are well known antioxidant molecules that may display a strong anti-proliferative
effect. Cha et al. (2008) isolated carotenoids from the marine microalga Chlorella ellipsoidea displaying
antiproliferative activity. Partially purified extracts of C. ellipsoidea inhibited HCT116 cell growth in
a dose-dependent manner, yielding IC 50 values of 40.73 µg/mL. In addition, treatment with Chlorella
extracts enhanced the fluorescence intensity typical of early apoptotic cell population in HCT-116 cells.
Astaxanthin, a red carotenoid accumulated by Haematoccocus pluvialis cysts, showed a potent antitumoural activity against oral and colon cancers. A few Dunaliella species also accumulate considerable
amounts of isoforms of β-carotene, which displayed a strong anti-proliferative effect against MCF-7 cell
line, along with astaxanthin (Guedes et al. 2011).
Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis, and
angiogenesis. Matrix metalloproteinases (MMP) are a family of zinc-dependent neutral endopeptidases
collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMP
can be detected in tumour tissue or in the serum of patients with advanced cancer and their role as
prognostic indicators in cancer has been assessed. Also, MMP inhibitors are in clinical trials with
cancer patients (Vihinen and Kähäri 2002). 6,6’-bieckol is a phloroglucinol derivative isolated from
the marine alga Ecklonia cava that inhibited MMP-2 and -9 gene expression by down-regulation of
NF-κB. Furthermore, 6,6’-bieckol suppressed the migration of HT1080 cell line (Zhang et al. 2010).
An Ecklonia cava phloroglucinol derivative, dioxinodehydroeckol, not only inhibited the proliferation
of human breast cancer cells (Kong et al. 2009), but also exerted a higher anti-proliferative activity
in MCF-7 human cancer cells as well as apoptosis induction in a dose-dependent manner. Treatment
with dioxinodehydroeckol induced caspase-3 and -9 activities, DNA repair enzyme poly-(ADP-ribose)
polymerase (PARP) cleavage, and pro-apoptotic (p53 and Bax) gene expression. It also led to a downregulation in Bcl-2 anti-apoptotic gene. In addition, the NF-κB family and NF-κB-dependent activated
genes were down-regulated (Kong et al. 2009). Apart from the inflammatory response, the inducible
transcription factor NF-κB plays an important role in the regulation of carcinogenic responses. Although
normal, NF-κB activation is necessary for cell survival and immunity, deregulated NF-κB expression is
common in cancer development (Folmer et al. 2008).
Prenylated bromohydroquinones are cymopol-related metabolites that are known to accumulate
in the marine chlorophyte Cymopolia barbata. One of these compounds, 7-hydroxycymopolone,
was investigated for cytotoxicity against three cancerous cell lines and one non-tumoural cell line.
7-hydroxycymopolone selectively impacted the viability of HT29 colon cancer cells (IC 50 = 19.82
μM) with similar potency to the known chemotherapeutic drug, fluorouracil (IC 50 = 23.50 μM). In
comparison, the effect on non-tumoural colon cells resulted in an IC 50 value of 55.65 and 55.51 μM
for 7-hydroxycymopolone and fluorouracil, respectively (Badal et al. 2012). The endemic New Zealand
brown alga Perithalia capillaris afforded a bis-prenylated quinone through bioactivity-directed isolation
that was potent at inhibiting the proliferation of HL60 cells (IC 50 0.34 µM; Sansom et al. 2007).
Fucosterol, identified as the most abundant phytosterol from the hexane fraction of Sargassum
angustifolium, was considered to be responsible for the cytotoxic effect of this extract against human