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Original Article

Prolific Anticancer Bioactivity of Algal


Extracts (Review)
Nadia Sharif*, Neelma Munir, Faiza Saleem, Farheen Aslam and Shagufta Naz

Department of Biotechnology, Lahore College for Women University, Lahore, Pakistan

SUMMARY

Now a days cancer incidences are in increasing trend and therefore


instant effective therapies are needed to control these malignancies.
Normally rapidly dividing cells are controlled by anti-cancer drugs,
but the normal cells are also affected and pattern in which it is
determines the side effects. The way in which the other cells are
affected determines the side effects of the individual drugs. These
side effects may be minimized by improving and new remedial
Address for preparations. These drugs could be of ethno botanical origin.
Correspondence Auspiciously numerous preceding readings have shown that the anti-
cancer activities of non-toxic biological macromolecules are higher
Department of than conventional chemotherapy drugs. Marine algae is obliged as
Biotechnology, Lahore significant sources of natural bioactive substances and there has now
College for Women emerged a new proclivity towards isolating and identifying such
University, Lahore, compounds and constituents from algae. This review article has
Pakistan. poised studies about algal anticancer agents.
E-mail: nadiasharif.s7
@gmail.com Keywords: Anticancer compounds, Cancerous cells, Inflammatory,
Proliferative, Mutagenic.

CANCER DEVELOPMENT, CAUSES,


AND TREATMENT
Cancer is most common and serious resistant to apoptosis, they overcome the
disease, it slaughters societies more than limitations on proliferation by avoiding
tuberculosis, malaria and HIV/AIDS replicative senescence and evading
combined1. A total of 12.5% of deaths differentiation, they are genetically unstable,
worldwide is due to cancer and 12.1 they are able to invade surrounding tissues
million cancer cases were in 2007, 45% and they are capable of metastasis3, 5. In
in developed countries and the remaining order for a cancerous tumor to develop,
55% in developing countries2-4. cancer cells must overcome replicative
There are six properties that make cell senescence and become immortalized
cells capable of cancerous growth; they are i.e. continue dividing indefinitely6. Tumors
not under the control of signals that are only considered to be cancerous if they
regulate cell proliferation, they are are capable of metastasis and colonizing

American Journal of Drug Delivery and Therapeutics www.pubicon.net


Sharif et al___________________________________________________ ISSN 2349-7211

surrounding tissue6,7. Even though most Remarkable and exhilarating biological


cancers are thought to be monoclonal, activities are displayed by microalgae like
cancer development takes place in many immunosuppressant, antitumor, anti-
years by and involves several progressions. microbial and antiviral activities which are
The original abnormal cell must undergo conspicuous targets of biomedical
some change that allowed it to grow much investigations11. Bioactive molecules with
faster than normal cells in the same tissue anticancer activities are one major group of
and this property had to be passed on to targeted compounds from microalgae.
subsequent daughter cells. For cancer to Hence, there is a need to extract natural
successfully develop, numerous but bioactive amalgams from algae.
independent changes must occur in this one More than 50 % of marine
cell3,4,8. cyanobacteria are possibly available for
Most cancers are thought to be a intending bioactive elements which are
result of genetic mutations in the DNA of powerful in either slaughtering the disease
the cancerous cells and these mutations can cells by instigating apoptotic demise, or
be a result of inherited mutations, influencing the cell signaling over the
metabolism mutations, cigarette smoking, enactment of the portions of protein kinase-c
diet (red meat, fried foods), alcohol, group of indicating chemicals. Isolation of
radiation, environmental pollutants, and cytotoxic antitumor substances from marine
infectious organisms i-e viruses, stress, organisms has been reported in several
obesity, and physical inactivity. These references during the last 40 years, while in
causative elements might act in sequence or recent years, hundreds of potential anti
together to pledge or stimulate cancers3,4,8. tumour agents have been isolated from
Chemotherapy is usually the first marine origin especially from marine algae
line treatment to cure cancers. Besides that, and12.
a group of drugs are used to kill or inhibit Compounds obtained from marine
the growth of cancer cells. These drugs are algae have assumed a vital part in the
allied through noxiousness that range from a improvement of a few clinically valuable
mild reaction to severe life-threatening anticancer managers. In most cases, the
illness. Many side effects of evaluation of anticancer potential of crude
chemotherapeutic drugs comprised baldness, extracts from different sea organisms has
vomiting, Canker sores, diarrhea, loss of been carried out by in vivo cytotoxicity tests
appetite, nausea and fatigue. Hence new in malignant cell cultures. The capacity of
anticancer agents should be investigated algal polysaccharides to incite cancer cell
from various resources. A lot of natural multiplication has been overall recorded.
antitumor amalgams or their byproducts are The epidemiological information is upheld
generally produced by blue-green algae9. by rat model studies exhibiting defensive
impacts of dietary kelps and other red and
BIOACTIVE MICROALGAL green algae against mammary tumors13.
ANTICANCER PIGMENTS Molecular and cellular level studies on algae
have indicated that algae derived bioactives
Free radicals are involved in the are potent cancer inhibitors. Documentation
induction of cancer formation in the human of new active cancer inhibiting agents have
body. On the other side it has been noted globally turn out to be a significant
that free radicals of vegetables and fruits strategy14.
doubles the protection against many types of
cancers by scavenging activity10.

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A variety of red algae as well as kelp production and down regulating


has anti proliferative and anti-inflammatory angiogenesis. It was also noticed that the
activities. In vivo and in vitro studies on selenium nanoparticles (SeNPs) with
seaweed constituents have been conducted Spirulina polysaccharides (SPS) may be
to explicate the antimutagenic mechanisms potential candidates against human cancers
of underlying the potential anticarcinogenic as chemo preventive and chemotherapeutic
effects of kelp and red algae against colon agents24 and polysaccharide from Porphyra
and breast cancers15,16. Some anticancer yezoensis are useful in the treatment of
agents of algal source are: human cancers25.
Polysaccharides extracted from
Polysaccharides Japanese kelp like Undaria pinnatifida,
Polysaccharides are utmost Hijikia fusiforme, Laminaria japonica and
bounteous amongst the characteristic natural Eisenia bicyclis were recognized as
bioactives produced by plants and they are forthcoming hostile to genotoxic elements.
generally present in algae, animals, Polysaccharides extricated from the brown
microorganisms and plants17,18. algae, Sargassum latifolium have significant
Polysaccrides are polymeric carbohydrate antitumor action against leukemia26.
structures that are formed by
monosaccharides linked by different Fucoidans
glucosidic19. Distinctive functional Polysaccharides - fucoidans that are
properties of polysaccharides are because of consisted of sulfated Lfucose with short of
their structure organized by their building what 10 % of different monosaccharides.
blocks20. Compared the Ecklonia cava Fucoidans are present in the cell walls of
polysaccharide compounds with commercial brown seaweed27. Fucoidan has
counterparts (BHA and BHT) and found that antiproliferative activities, although its
due to the high amount of polyphenol complete mechanism is yet not known. In a
contents it can suppress cancer cell study of28 10 mg/kg fucoidan was proved
proliferation. The polysaccharides isolated effective against metastatic tumor when it
from Spirulina sp. enhanced excision, was administered in Lewis lung
unscheduled DNA synthesis, radiation adenocarcinoma affected mice.
damaged DNA repair activity and exhibited Tumor size and growth could be
enhanced activity of endonuclease controlled by the polyanionic
significantly. DNA synthesis of sarcoma polysaccharides due to their antiproliferation
180, ascetic hepatoma cells and proliferation and anti-angiogenesis actions towards tumor
of ascitic hepatoma cells of mice is also cells29. These substances are also involved
inhibited by it21. in anti-cancer activity through ERK and
Calcium spirulina (Ca-SP) is a caspase pathways against human HS-Sultan
polysaccharide of Spirulina platensis cells30. Fucoidans are also able to enhance
inhibited tumor invasion and metastasis22. the immunomodulatory activity to restrain
Observed that the acidic polysaccharides in the diffusion and development of tumour
S. platensis are involved in macrophage - cells as they mediate the destruction of
tumor necrosis factor- (TNF-) dependent tumors by NK cell and type 1 T helper (Th1)
tumoricidal activity23. Found that the cell responses31. When fucoidan is used at
Spirulina polysaccharides suppress the 25 mg/kg dose, several types of auto-
glioma cell (murine RSV-M) growth via immune disorders and tumors are reduced
partial regulation of interleukin-17 due to the cyclophosphamide toxic effect28.

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Due to antiproliferative bioactivity, fucoidan inflammatory and anticancer properties and


is also noted as an active principal of CpoF. prompts in vitro apoptosis35. The increased
This sulfated polysaccharide is composed of phycocyanin of S. platensis induces
fucose with small amount of galactose. apoptosis by the expression of CD59
Molecular weight and sulfate contents are proteins in HeLa cells36. The apoptosis is
directly related to their anticancer activity. It induced by C-PC in HeLa cells by activating
is documented that the anticancer activity of apoptosis enzymes, caspases 2, 3, 4, 6, 8, 9,
fucoidans is increased when it is hydrolyzed and caspase - 10. The cytochrome c that is
for 5min with HCl in boiling water. released from the mitochondria into the
Conversely the anticancer activity is slightly cytosol cause C-PC-treated HeLa cell
improved when fucoidans are hydrolyzed in apoptosis (in vitro). The survival rate of
a microwave oven. So it is concluded that mice with live tumor cells is increased by
fucoidans anticancer activity might be the oral administration of PC of Spirulina
enhanced considerably by lowering the and S. platensis C-phycocyanin (C-PC)
molecular weight when they are inhibit the growth and cell viability of
depolymerized at mild conditions32. human leukemia K562 cells. PC is a
Fucoidan was tested for its efficiency potential cancer chemopreventive37.
and it was found that it increases Spirulina platensis (selenium-
Smac/Diablo and cytochrome c release from enriched) derived selenium-containing
the mitochondria as well as its enhanced phycocyanin (Se-PC) is a strong anticancer
mitochondrial membrane permeability. It agent on human breast adenocarcinoma
was also observed that the levels of Mcl-1 MCF-7 cells and human melanoma A375
decreased, whereas death receptor 5 cells. The Se-PC induces apoptosis by
proteins, truncated Bid proteins, TRAIL, accumulation of sub-G1 cells, and nuclear
Fas, and Bak were increased in fucoidan condensation, DNA fragmentation in both
treated cells33. MCF-7 cells and A37538. Spirulina
platensis display potential effect on the
Phycocyanin (PC) immune system and immune response and
Phycocyanin is currently used in it contributes some extent in treating
Japan and China as a regular coloring agent diseases and killing of cancerous cells.
in dairy and dietary products like gums, The purified c-phycocyanin and
candies, jellies, beverages (e.g. Pepsi blue polysaccharides of Spirulina platensis
and also in cosmetics such as lipsticks, influence the proliferation and
eyeliners and eye shadows. Phycocyanin is differentiation of committed hematopoietic
light and heat sensitive, but it is a more progenitor, can lower the anemic degree of
epitome blue colorant than indigo and mice. and enhances the immune response by
gardenia and it gave more bright blue color activating macrophage functions, IL - I
in jellies and candies34. Algal Phycocyanin production, phagocytosis and particularly
is also useful in the treatment of different by primary. Therefore the part of PC to
types of cancers25. enhance efficiency of the immune response
The phycocyanin isolated from S. is important in treatments and prevention of
platensis exhibited anticancer activity all types of cancers39.
against squamous cell carcinoma. C-
phycocyanins (C-PC) is a major biliproteins Chlorophyll
of S. platensis has radical scavenging and Carotene, chlorophyll and lutein
antioxidant properties. It exhibits anti related compounds derived from algae

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strains have been accounted for solid ant


proliferative bioactivity in vitro and in vivo. Carotene
Tumor preventive impacts of chlorophyll One of the utmost recognized
and its subordinates have been widely important active antitumor agents are beta
concentrated on, with specific accentuation carotene. Spirulina is very rich in beta-
on their in vitro anticarcinogenic impact carotene. Beta carotene significantly
against various ecological and dietary inhibits the formation of squamous cell
mutagens. Chlorophyll-a and chlorophyllin- carcinoma. Spiulina, Dunaliella algae
a have displayed huge concealment against prevents tumor development. Studies related
the instigation of ornithine decarboxylase in to use of beta carotene on animals indicated
mouse skin fibroblasts created by a tumor slighter however, statistically momentous
promoter utilizing within vitro cell culture decrease in tumor size and number.
tests40,41.
Fucoxanthin
Pheophytin A brown algae carotenoid known as
Pheophytin, secluded from E. fucoxanthin is recognized to exhibit
prolifera accounted for to illustrate the potential antitumor activity. It also abridged
strong oppressive impact against artificially the human colon cancer cell lines by
affected mouse skin tumorigenesis from end inducing the fragmentation of DNA.
to end concealment at launch and limited Fucoxanthin is involved in decreasing the
time stages. E. prolifera derived apoptosis suppressing protein (Bcl-2) level,
Pheophytins also exhibited higher it induced apoptosis in human prostate
suppressive activity than chlorophyll a in S. cancer cells (PC-3, DU 145 and LNCaP)
43,44
typhimurium and mouse skin . In a re-sensitizing test for drugs it was
tumorigenesis20,41,42. found that fucoxanthin overcome drug
resistance45. Though the complete
Carotenoids mechanism is yet not known, but according
Natural fat-soluble pigments known to researchers in several cancer cells
as carotenoids, provides bright pigmentation apoptosis may be induced by the prooxidant
to and animals plants. Numerous actions of oxygen, alkali and acids with
carotenoids, in the same way as a-carotene, double bonds and 5, 6-monoepoxide of
astaxanthin, beta-carotene, zeaxanthin, fucoxanthin33,41.
lycopene, canthaxanthin, beta- Compared46 and found that the
cryptoxanthin, lutein and fucoxanthin have inhibitory activity of fucoxanthinol and
been demonstrated to have against cancer- fucoxanthin was higher than astaxanthin and
causing action in a few tissues. Preclinical b-carotene. It was observed that fucoxanthin
studies have demonstrated that a few induced apoptosis in human leukemia cells
carotenoids have powerful anticancer (HL-60) by activation of central executioner
impacts both in vitro and in vivo models. of the apoptotic pathway that is caspase-3, -
Since chemoprevention is a standout 8 and -944.
amongst the most critical methodologies in
the control of malignancy improvement, Siphonaxanthin
sub-atomic component based disease A marine carotenoid Siphonaxanthin
chemoprevention utilizing carotenoids derived from green growth has as of late
appears to be an alluring methodology been exhibited to lessening outflow of Bcl-2
(Tanaka et al., 2012). and astoundingly upgraded initiation of

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caspase-3 alongside up-controlled marine crinoids Comantheria rotula


representation of Gadd45 and Dr5 in utilizing Bioassay-guided fractionation and
human leukemia (HL-60) cells. They have altogether repressed hypoxia instigating
additionally reported that siphonaxanthin component (HIF) action, however, vascular
inferred from Codium fragile are more endothelial development variable (VEGF),
strong development inhibitor against HL-60 the target quality of HIF was not
cells than fucoxanthin (Farooqi et al., significantly curbed. In any case these
2012b; Ganesan et al., 2011a). crinoids colors differentially stifled the
The structural contrasts between development of certain tumor cell lines (Dai
these two carotenoids are fucoxanthin et al., 2006).
contains epoxide and an allenic bond in its Sodwanone a triterpenoid from a
structure, though siphonaxanthin does not South African type of the marine wipe was
contain those useful gatherings; additionally tried to be powerful in
notwithstanding, siphonaxanthin has an restraining HIF-1 initiation in PC-3 prostate
extra hydroxyl gather on the nineteenth tumor cells (Dai et al., 2007).
carbon iota. Since esterified type of
siphonaxanthin indicated lower inhibitory Stypodiol diacetate
impact, recommending that the vicinity of 14-keto-stypodiol diacetate is a
that hydroxyl gathering is helping the solid medication extricated from the green growth
inhibitory impact of siphonaxanthin Stypopodium flabelliforme and was
(Ganesan et al., 2011a). In the meantime, demonstrated to upset microtubular
hostile to proliferative impact and apoptosis association furthermore restrained cell
affectation by fucoxanthin in human colon expansion in DU-145 human prostatic
malignancy cells (Caco-2, HT-29 and DLD- cells47.
1) were seen by (Hosokawa et al., 2004).
Glycoprotein
Pheophytin Glycoprotein of Capsosiphon
Pheophytin, segregated from E. fulvescens, green ocean green growth impels
prolifera has been accounted for to show the apoptosis in human gastric tumor (AGS)
powerful suppressive impact against cells Kim et al. Fucose-containing sulfated
artificially instigated mouse skin polysaccharides (Fcsps) extricated from tan
tumorigenesis through concealment at the macro-green growth is likewise archived to
start and special stages (Athukorala et al., affect apoptosis48, 51.
2006b). Investigations of tan green growth
E. prolifera determined Pheophytins have demonstrated that glycoproteins from
showed higher suppressive action in S. Laminaria japonica and fucoidans from
typhimurium and mouse skin tumorigenesis Sargassum hornery, Eclonia cava, and
than chlorophyll a. These discoveries, Costaria costata had hostile to disease
recommend that porphyrin mixes impacts on human colon malignancy cells.
determined marine green growth may have a Heterofucans from Sargassum filipendula
vital chemopreventive movement against showed against proliferative consequences
carcinogenesis (Pangestuti and Kim, 2011). for cervical, prostate, and liver growth cells.
A carotenoid fucoxanthin cool restrain the
Benzochromenone development of Lncap prostate growth cells
Benzochromenone is a colorant by capturing these phones in the G1 stage by
acquired from a dynamic concentrate of the means of the Gdd45a and SAPK/JNK

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pathways. Investigations of blue green spinifera and dinoflagellates. At the point


growth have affirmed the opposition to when the natural conditions empower the
disease impacts of Spirulina arrangements development of these algal species, YTXs
recombinant glycoproteins, particularly can aggregate in the water supply and inside
microcystis viridis lectin (MVL), and the palatable tissues of bivalve molluscs,
cryptophycin52-54. including scallops, mussels, and mollusks,
consequently empowering the passage of
Meroditerpenoids YTX into the evolved way of life.
Viability of meroditerpenoids Yessotoxins acquired from red tide green
segregated from the tan alga Stypopodium growth, Protoceratium reticulatum are
flabelliforme were tried and it was exhibited successful regarding affectation of
that it demonstrates impressive movement apoptosis56,57.
against distinctive disease cell lines (Areche
et al., 2009b; Gamal and Ali, 2010; Pereira Elatol
et al., 2011). Meroterpenoids are of blended Elatol also have antitumor activity
biogenesis containing terpenoid and non- and various studies have confirmed that
terpenoid inferred parts. This wide denition Laurencia microcladia derived elatol
could incorporate the immense number of reduces tumour growth in C57BL6 mice48,58.
straightforward prenylated phenolics yet is
typically held for mixes where the terpenoid Bis (2, 3-dibromo-4, 5-dihydroxybenzyl)
section embodies a huge piece of the atom. ether (BDDE)
The polyprenylated quinones and BDDE bromophenol compound that
chromanols typied by the ubiquinones and obtained from marine algae have persuasive
tocopherols are plainly of blended apoptotic activity in K562 cells48,59.
biogenesis yet the metabolites of Aspergillus
ustussuch as Austin could be mixed up for Sargachromanol E (SE)
sesterterpenoids. Truth be told these SE, chromene derived from
metabolites have been demonstrated to be Sargassum siliquastrum inhibit HL-60 cells
inferred from a sesquiterpenoid part and a at a specific concentration. The compound
sweet-smelling polyketide piece55. was additionally noted to impel apoptosis by
means of caspase 3 enactment60. Kelp and
Stypotriol triacetate red algal extracts have potential anti-
This polycyclic meroditerpenoid, the carcinogenic and antimutagenicity against
complete setup of which was as of late breast and colon cancer16,61.
decided, was likewise separated from the
kelp Stypopodium flabelliforme (Areche et Cannabinoids
al., 2009a). Conventional chemotherapies
produce toxic effects, but Cannabinoids do
Yessotoxins not produce such effects and these are
Yessotoxins (YTXs) are a gathering usually well tolerated. Cannabinoids of
of lipophilic sulfated polyether intensifies Cannabis sativa stimulate appetite and
that are structurally identified with prevent vomiting; pain and nausea in cancer
brevetoxins and ciguatoxins. They are patients so have palliative effects. These
delivered by various algal strains, especially compounds also modulate key cell-
the Protoceratium reticulatum, signalling pathways to inhibit the growth of
Lingulodinium polyedrum, Gonyaulax tumour cells in animal models and culture62.

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regression. Some monoterpenes have been


Triprenylated toluquinones and toluhydro- patented as potential chemotherapeutic
quinones drugs and in addition to having anti-cancer
Leminda millecra and Arminacean activity these compounds are also capable of
nudibranch derived toluhydroquinones and sensitizing select tumors to radiation71. (See
triprenylated toluquinones are involved in table 1.)
apoptosis of esophageal cancer cells63.
CONCLUSION
Monoterpenes
Monoterpenes (e.g., linalool) are Chemotherapeutic agents are unable
used as flavors/fragrances in food additives. to completely control the cancer stem cells,
Camphene, -pinene and monoterpenes which are inherently resilient and become
which are produced by numerous plants are repopulated subsequent to chemotherapy. But
involved in inhibiting the early root growth only few or no side effects are observed when
and seed germination in several plant natural anticancer agents are used. Therefore,
classes64,65. Halogenated monoterpenoids are the prevention of cancers by the identification
also found in many marine organisms. It has of distinctive cancer chemotherapeutic has
been revealed by studies that algal Quinones turn out to be a vital worldwide approach.
and halogenated monoterpenes are enable to This mini review was made to convey the
prompt in vitro apoptosis in breast cancer glare of publicity of current examinations
cells66. concerning the likely effects of bioactive
Halogenated monoterpenes are also components of algae on cancer. It can be
produced by Plocamium, Porteria and concluded from previous studies on algae
Ochtodes algal species. Halogenated cancerous bioactivity that microalgae is
monoterpene, isolated from Portieria probable to develop anticancer drug as it is a
hornemannii, containing both bromine and product of nature. However, further studies
chlorine groups was shown to have high need to be performed to fully exploit its
levels of cytotoxicity against brain, colon anticancer properties such as determination of
and kidney tumours. Species of the the nature of cell death caused by the extract
Plocamium genus produce both linear and or visual detection and confirmation of
cyclic halogenated monoterpenes as apoptosis.
secondary metabolites67. These compounds
have been demonstrated as having anti- ACKNOWLEDGEMENT
cancer activity in human oesophageal cancer
The authors want to thank the
cell line WHCO168,69. In another study, four
financial supports from Higher Education
halogenated monoterpenes from Plocamium
Commission (HEC) Pakistan (1500006861/
cartilagineum showed anti-cancer activity
3244).
against colon adenocarcinoma cell line
SW480 and cervical adenocarcinoma cell
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Table 1. Algae-derived natural anticancer extracts41,79,72

S. No. Extracts Source References


73
1 Siphonaxanthin Codium fragile
74
2 Kappa-carrageenan Kappaphycus striatum
75
3 Alginate Sargassum vulgare
76
4 Kahalalide F Bryopsis sp.
77,78
5 Plocoralide A/B/C/D/E Plocamium corallorhiza
71,79
6 Plocoral A/B Plocamium corallorhiza
80
7 Sargaquinoic Acid Sargassum heterophyllum
79
8 Plocornulide A Plocamium cornutum
79
9 Plocornulide C-erythro Plocamium cornutum
79
10 Plocornulide C-threo Plocamium cornutum
81
11 Fucoxanthin Undaria pinnatifida
11
12 Apratoxins Cyanobacteria
82
13 Cyptophycin 1 Nostoc linckia
83
14 Caulerpenyne Caulerpa sp.
84
15 Fucoidan Ascophyllum nodosum
85
16 Phycocyanin Spirulina sp.

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