ANTICANCER

Introduction

Cancer :Abnormal, unwanted multiplication of cells,

• It is a disease of cells characterized byUncontrolled proliferationDedifferentiation(anaplasia)InvasivenessMetastasis

Categorized based on the functions/locations of the cells

Carcinoma - skin or in tissues that line or cover internal organs. E.g., Epithelial cells. 80-90% reported cancer cases are carcinomas.

Sarcoma - bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Leukemia - White blood cells and their precursor cells such as the bone marrow cells, causes large numbers of abnormal blood cells to be produced and enter the blood.

Lymphoma - cells of the immune system that affects lymphatic system.Myeloma - B-cells that produce antibodies- spreads through lymphatic system.Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.

Common etiological factors

• Viruses :EBV,HBV• Environmental and Occupational factors• Diet and habits• Genetic factors• Drugs :immunosuppressant

Basic mechanism of cancer development

Activation of proto-oncogene's- ex:BCL2,RAS

Inactivation of tumor suppressor genes:P53

Types of cancer

Benign • Slow growth• Resemble normal cells

• Localized • Not harmful

Malignant • Fast • Don’t • Invasive and metastatic • Harmful if left untreated

CELL CYCLE

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LIST OF ANTI CANCER PLANTS• ASHWGANDHA Withania somnifera Linn.• MANJISTHA Rubia cordifolia Linn. • DARUHALDI Berberis aristata DC.• TULSI Ocimum sanctum Linn.• HALDI Curcuma longa Linn.• GARLIC Allium sativum Linn.• SAHIJAN Moringa oleifera Lam.• ARKA Calotropis procera (Ait) R. Br.• CHITRAKA Plumbago zeylanica Linn.• TALISPATRA Taxus baccata Linn.

Ashwagandha• Botanical source: dried

mature roots of Withania somnifera (L.) Dunal

• English name : Indian ginseng, Winter cherry

• Family    :  SolanaceaeCommon Indian names : Hindi    :  AsgandhSanskrit : Ashvagandha,

Balada, Gandhpatri,

Classification of Withania somnifera

• Kingdom : Plantae• Division : Angiosperms• Class : Dicotiledoneae• Order : Tubiflorae• Family : Solanaceae• Genus : Withania• Species : somnifera

Habitat/Distribution

• The genus Withania is reported to have 23 species out of which, Withania somnifera is of high medicinal value. Withania somnifera is cosmopolitan and grows throughout the drier parts and subtropical regions. The wild growth of this species has also been reported from India, Pakistan, Afghanistan, Philistine, Egypt, Jordan, Morocco, Srilanka, Spain, CanaryIsland, Eastern Africa, South Africa. These areas represent wide variations of soil, rainfall, temperature and altitude

Morphology Straight , unbranched

outer surface buff to gray yellow with longitudinal wrinkles . fracture, short and uneven dry root cylindrical, gradually tapering down with a brownish white surface and pure white inside when broken.

Microscopy

A- CorkB - CortexC – EndodermisD – Pericycle E – PhloemF – Medullary ray G - Pith

Chemical constituent

Alkaloids :isopelletierine, anaferine, cuscohygrine, anahygrine, steroidal lactone: withanolides, withaferins and saponins, withanine, somniferine, somnine, somniferinine, withananine, pseudo-withanine tropane, pseudo-tropine, choline, anaferine, anahydrine,

Uses • Antibiotic • Antitumor• Arthritis • Anxiety  • Trouble sleeping (insomnia)• Tuberculosis , asthma• Leukoderma ,bronchitis• backache, fibromyalgia, menstrual problems• hiccups, and chronic liver disease.

Anticancer activity• Colon cancer• Breast cancer• Lung cancer • Skin cancer• Blood cancer• Prostate cancer• Renal cancer• Pancreatic cancer• Fibrosarcoma

Anticancer Activity of Withania Somnifera

• Hydro alcoholic (1:1) sample of Withania Somnifera (leaves) were prepared and tested for their Cytotoxic activities against cancer cell lines (MCF7, A549and PA1) with standard Doxorubicin. The most essential reason of this study is to estimate cytotoxicity of certain important Indian medicinal plants with facilitate of MTT assay.

• Concentrations are set of each plant extract which are 100 µg/ml, 10 µg/ml , 0.1 µg/ml, 0.01 µg/ml and 5-10×10 3 cells/ml are taken into each well which are exposed to different Concentrations of Withania Somnifera (leaves) for 96 hr and then treated with MTT. For MTT absorbance in use at 570 nm. From IC50 values of MTT assay of Withania Somnifera (leaves) for MCF7, A549 and PA1 cancer cell lines, from this it may conclude that Withania Somnifera (leaves)shows efficient cytotoxicity on MCF-7 (10 ± 1 µg ) than PA-1 (13 ± 1 µg) and A-459 (11± 1 µg) cancer cell line.

Chitraka

ENGLISH NAME: Leadwort

HINDI NAME: Cheeta , Chitrak

Biological source: dried roots of Plumbago zeylanica Linn. Family Plumbaginaceae

Geographical source

• This is perennial herb grow in shady places in the garden and found in Sri Lanka (Ceylon) and parts India, which include Bengal, Uttar Pradesh, and Southern India.

Morphology

Straight, long, unbranched or slightly branched root are always observed with or without secondary roots, the texture of the roots are unbroken and smooth, roots are usually very strong and they have a distinctive odour with acrid and bitter taste

Microscopy

Chemical constitutes

• The roots contain an alkaloid called plumbagin, a natural napthaquinone (5-hydroxy-2-methyl-1,4- naphthoquinone)Its other constituents in roots are chitranone, zeylanone, dihydrosterone, 2- methyl naphthaquin, plumbazeylanone and terpenoids, lupeol and teraxesterol.

Uses• Anticancer,• Anti-fertility activity • Antimicrobial activity• Antimalarial• Antioxidant activity• Cardiotonic,• Antifertility action• Antibiotic and • Antineoplastic

Anti cancer activity of Chitraka  Plumbagin inhibited the growth of Panc-1 and 

Bxpc-3 cells in a dose-dependent and time-dependent manner. Liu's staining and transmission electron microscopy demonstrated morphological changes resembling apoptosis in Panc-1 ceils treated with piumbagin. The degree of apoptosis was assessed by measuring the proportions of sub-G1, annexin V+/propidium iodide-, and terminal-deoxynucleotidyl-transferase-mediated-nick-end labeling (TUNEL)+ cells, and a significant increment in apoptotic cells was observed. 

Exposure to piumbagin caused theupregulation of Bax, a rapid decline in mitochondrial transmembrane potential, apoptosis-inducing factor overexpression in cytosol, and the cleavage of procaspase-9 and poly ADP-ribose polymerase. Activation of caspase-3, but not caspase-8, was evidenced by fluorometric substrate assay. Pretreatment with caspase inhibitors did not block plumbagin-induced apoptosis. Alternatively, it is possible that piumbagin down-regulated phosphoinositide3-kinase activity through a negative feedback mechanism

In an orthotopic pancreatic tumor model, piumbagin markedly inhibited the growth of Panc-1 xenografts without any significant effect on leukocyte counts or body weight. Conclusion: Piumbagin may induce apoptosis in human pancreatic cancer cells primarily through the mitochondria-related pathway followed by both caspase-dependent and caspase-independent cascades. It indicates that piumbagin can be potentially developed as a novel therapeutic agent against pancreatic cancer

Manjistha Synonym: English name: Indian MaddarHindi name: Manjitha, ManjitBiological source: dried stem of

climber known as raktapushpi Rubia cordifolia Linn. (Fam. Rubiaceae).

Geographical sourceIt is found in afganistan, nepal, and iran upto 

altitude of 2700m. It is also found abundant in konkan. 

Morphology

Stem slender, more or less cylindrical, slightly flattened, wiry, about 0.5 cm thick, brown to purple coloured surface scabrous, stiff and grooved with longitudinal cracks; prickles present in the immature stem; nodes distinct having two leaf scars, one on either side; fracture, short.

Microscopy

Chemical constituents

• It contains glycoside, manjisthin, purpurin, resin and red dye rubiadin( 1:3 dihydroxy-2 methyl anthraquinone), xanthopurine, psudopurpurin

Uses

It is used in the treatment of leucoderma,gauty arthritis and skin pigmentation.

Helps to gain lustre and glow of skin and aids to remove pimples, freckles and discoloration.

In ayurveda, it is used as blood purifier.It is used in textile industries for dyeing of

fabrics

In vitro Anticancer Activity of Rubia Cordifolia Against Hep G

32 Cell Linein vitro cytotoxicity  of  Rubia cordifolia against  Hep 

G32  (human  Hepatocellular  carcinoma)  cell  line using  XTT  assay.  Methanol  fraction  of  Rubia cordifolia extract exhibited potent inhibition of Hep G32  cell  line with  IC50  value of  28.07 μg/ml while was  found  to  be  less  cytotoxic  against  normal human kidney cells with  IC50 value more than 100 μg/ml  displaying  safety  for  normal  cells.

DARUHRIDRA

• Hindi. : Daruhaldi,Darhald English: Indian berberryBiological Source:This consistsof dried stem of Berberis aristata, 

Family: BerberidaceaeGeographic Source:From northwest,Himalayas,east ward to 

Bhutan.Distribution:J & K, Himachal 

Pradesh, Uttar Pradesh   (GarhwalHimalayas). Nepal, Bhutan.

Macroscopic Characters• Size: 0.4 - 0.8 cm thick• Shape: cylindrical• Colour: pale yellowish brown• Odour: aromatic • Taste: bitter

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Microscopical characteristics of Berberis aristata

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Phytochemical Investigation

• The  chemical  analyses  of  the  stems  of  Berberis aristata . showed the presence of alkaloids, amino acids, flavonoids, phenol,  proteins,  sterols/terpenes,  reducing  sugars,  non-reducing  sugars  and  tannins.These  secondary  plant metabolites are known to possess various pharmacological effects  and may  be  responsible  for  the  various  actions  of Berberis aristata. 

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PHYTOCHEMICAL CONSTITUENT

The chief constituent of the roots and stem bark of Berberis aristata is an alkaloid Berberine. other constituents including berbamine,  aromoline,  palmatine  oxyacanthine  and oxyberberine are also isolated. a

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• Major Compound→

Berberine →

Berbamine →

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• Palmatine → 

• Minor compound-

Oxyacanthine ,Aromolin, Karachine

PHARMACOLOGICAL ACTION [22]

►Anti-diarrheal activity

►Anti-fungal activity

►Antihepatotoxic action

►Antihistaminic and anticholinergic activity

►Anti-inflammatory activity

►Anti-microbial activity

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ANTI CANCER ACTIVITY

• Here is a list of different types of cancers that Berberis aristata may be prevent and help fight> Lungs> Liver> Prostate> Breast

Berberine Berberine,  an  isoquinoline  plant  alkaloid  is  obtained  from  different plant  species  of  Berberis  aristata  .They  showed  anti-cancer  activity both  in-vivo  and  in-vitro  report  show  that  berberine  has  found effective against osteosarcoma, lung, liver, prostate and breast  cancer

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      The  potential  anticancer  activity  of  berberine    has  always  been  a subject  of  considerable  interest  because  of  its  known  ability  to interact  with  nucleic  acids.  Its  ability  to  bind  specifically  to oligonucleotides and to stabilize DNA triplexes or G-quadruplexes via telomerase  and  topoisomerase  inhibition  accounts  for  its  anti proliferative activity. The predominant interaction between berberine and  double-stranded  or  single-stranded  DNA  is  electrostatic.  In addition,  the  autophagic  marker,  microtubule-associated  protein-1 light  chain  3  (LC3)  was  modified  after  administration  of  berberine hydrochloride in the human lung cancer cell line.

Berbamine- Berbamine, a bisbenzylisoquinoline alkaloid .It was found thatberbamine effectively causes cell apoptosis  and resistant Ph+chronicMyeloid leukemia cells. They work by inducing caspase-3dependentapoptosis of leukemic NB4 cells by the survivin-mediated pathway .

KATUKI

• Biological source: dried rhizomes of the plant Pichrorhiza Kurroa (Fam. scrophulariaceae), cut in small pieces and freed from attached root lets

• English : Hellebore• Hindi : Kutki

Geographical source 

Well distributed in the upper himalayas and also in china . It is also growing naturally 

Macroscopic Characters

• Colour – the rhizomes are deep greyish-brown in color, externally white, blackish internally with whitish-wood.

• Odour – slight, unpleasant• Taste –bitter• Size- 3 to 5 cm in length and 0.5 to 1 cm in diameter• Shape – cylindrical pieces with longitudinal

wrinkles and annulations at the tip.

MICROSCOPY

The transverse section of rhizome showed 20-25 layers of cork consisting of tangentially  elongated,  suberised  cells  and  cork  cambium.  The  cortex  is multilayered and vascular bundles are present in cortex. The vascular bundles are  surrounded  by  single  layer  endodermis  of  thick-walled  cells.  The secondary phloem is composed of phloem parenchyma and a few scattered fibres  and  2-4  layered  cambium.  The  secondary  xylem  consists  of  vessels, tracheids, xylem fibers and xylem parenchyma. The tracheids are long, thick-walled,  lignified and more or  less cylindrical. The xylem parenchyma is thin-walled,  polygonal  in  shape  and  centre  occupied  by  small  pith  consisting  of thin-walled cells. It is simple round to oval shape containing starch grains. 

TRANSVERSE SECTION OF RHIZOME

CHEMICAL CONSTITUENTKUTKOSIDE,KUTKIOL,KUTKISTEROL,KUTKIN,PICRORHIZ

IN,PICROSIDE,D-MANNITOL ETC.

• PARTS USED: Root,Underground stem( Rhizome, root) 

Use: • Picrorrhiza is used as valuable bitter tonic, ant 

periodic, febrifuge and stomachic and laxative in large doses. 

• Alcoholic extract of root is found to have antibacterial effect.

• The drug is found to useful in treatment of jaundice• Kutkoside has been found to be a potential 

hapatoprotectant.

ACTIVITY

• To   determine  the  anticancer  and  cytotoxic  potential  of  Nano  encapsulated extract formulation from rhizome of Picrorhiza kurroa enriched with Apocynin, caffeic  esters  and  cucurbitacins  aglycone  compounds,  to  produce any  cytotoxic  effect  on  mammalian  cell  lines.  The  test  conducted  using  MTT  method  using  human  hepatocarcinoma  cells  (HepG2)  and  Madin Darby Canine Kidney (MDCK) cell lines as part of the in vitro preclinical characterization of  compound. 

More than 100% increment in cell killing at a concentration of  100µg/ml  recorded  in  both  the    cell    lines,    52.5%   cytotoxicity    in    HePG-2    cell    line    was    recorded    at   0.1µg/ml    concentration,  whereas    50.4%    cytotoxicity   assessed  in  MDCK  cell  line  at  1µg/ml  of  Formulation  concentration.  Exhibited  LC50    value  of  Formulation  in HePG-2 and MDCK cell  lines were recorded 1.2 µg/ml and 4.14µg/ml  respectively.  Cytotoxic  effect  against  HePG-2 cancer  cell  line  is  considered  as  a  predictive  anticancer activity indicator also, where Doxorubicin is a standard anti-cancer  agent  which  is  a  highly  cytotoxic  drug.  MDCK cytotoxicity  results  support  that  formulation  is  less cytotoxic in normal cell lines, as MDCK is a Non -Cancerous cell line.