Studies on Anticancer Agents from Natural Sources. The Tabernaemontana Divaricata (L.) R. Br. ex Roem. & Schult.


Abstract, 2014

69 Pages, Grade: 1


Excerpt


CONTENTS

-INTRODUCTION

-LITERATURE REVIEW

-OBJECTIVES AND PLAN OF WORK

-EXPERIMENTAL WORK
-DOCKING STUDIES
-PHYTOCHEMICAL STUDIES
-PHARMACOLOGICAL STUDIES

-SUMMARY AND CONCLUSION

-REFERENCES

INTRODUCTION

CANCER

- Cancer is abnormal growth of cells generally called as malignancy.

- There are different types of cancer, ranging over 100.  Reasons of cancer: mutation and abnormal activation of genes

- Only a small fraction of mutated genes can develop into cancer. (Guyton and Hall)

- Main reason of mutation

- Radiations
- Chemical irritants
- Hereditary factors
- Viruses

illustration not visible in this excerpt

Prevalence of different types of cancer worldwide, 2012

(Source: World Cancer Research Fund International,

http://www.wcrf.org/int/cancer-facts-figures/worldwide-data)

BREAST CANCER

- Breast cancer may originate either in ducts or in glands.
- Two types: Lobular carcinoma and ductal carcinoma.
- If the cancer crosses immediate crossing, it is called invasive carcinoma (Riche and Swanson, 2003).
- Stages of breast cancer
- Stage 0- tamoxifen therapy
- Stage 1- NMT 1 inch in diameter. Not present outside breast
- Stage 2A- 1 inch
- Stage 2B- 1-2inch, may or may not spread to lymph nodes
- Stage 3A- 2 inch, spread to axillary nodes
- Stage 3B- may spread to lymph nodes attached to breast
- Stage 3C- may spread to collar bone, neck, lymph nodes in breast
- Stage 4- spread to other organs like bones, lungs and brain

ESTROGEN RECEPTOR

- Estrogens exert their activity by binding with the estrogen receptors, nuclear receptor superfamily.
- The estrogen receptor Į (ERĮ) helps in the growth and differentiation of skeletal, neural, cardiovascular and reproductive tissues.
- ERĮ ligands bind mostly to the C-terminal ligand binding domain.
- Helix 12 in DES complex consists of residues from 538 to 546, in OHT complex the helix 12 consists of 536 to 544 (Shaiu et al, 1998).

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MCF-7 CELL LINE

- Isolated from 69 year old Caucasian woman’s cancer cells
- Malignant adenocarcinoma in a pleural effusion was removed in the second surgery, from which MCF-7 cell lines were prepared.
- Initially 85 karyotypes in the chromosomes. Later it was reduced to 69.
- Characteristics: sensitive to cytokeratin, Tumor necrosis factor alpha (TNF alpha) can inhibit growth.

Desmin, endothelin, and vimentin are unresponsive to MCF-7 cell line

(www.mcf7.com).

Reproduced from:

http://mcf7.com/wp-content/uploads/2014/08/mcf-7G.jpg

http://mcf7.com/wp-content/uploads/2014/08/MCF-7-2.jpg 9

TABERNAEMONTANA DIVARICATA

illustration not visible in this excerpt

LITERATURE REVIEW

LITERATURE: ANTICANCER PLANTS

- Masfria et al. (2013) -anticancer properties of ethanolic extract of Rhaphidophora pinnta.

- Valiyari et al. (2013) -anticancer and cyctotoxic activity of Scrophularia oxysepala.

- The dichloromethane and methanol extract found to have the cytotoxic activity.
- Reason- induction of apotosis

- Elkady et al. (2012) -anticancer properties of Zingiber officinale.

- Methanolic extract was having antiproliferative effect.

- Kundu et al. (2012)- antimetastatic property of Colocasia esculenta. Water extracts of the plant showed significant antimetastatic property in tumor induced mammary glands.

- Sepehr et al. (2011)- anticancer effect of extracts from Cuscuta kotschyana on MCF 7 cell line. The flavonoids extracts were tested for anticancer properties.

- Duarte et al. (2010) - isolated two alkaloids from Pterogyne nitens, namely pterogynine and pterogynidine tested for infiltrating ductal carcinoma cell line.

- They found that both the alkaloids have significant anticancer properties by inducing programmed cell death.

- Orawan et al. (2005)- isolated belalloside A, belalloside B, and belamphenone and thirteen known compounds from the rhizomes of Belamcanda chinensis. Belamphenone was found to stimulate MCF-7 cell lines.

- Lee et al. (2003)- isolated styrylpyrone derivative from Goniothalamus species showed antiproliferative activity using MCF-7 cell line.

- Reason: regulation of Bax protein expression

- Julio et al. (2000)- isolated glycoconjugate from Crocus sativus.

- The compound showed an IC50 value of 22µg/ml when tested for anticancer activity against breast cancer using MCF-7 cell line.

- Surendra et al. (1997) has found that curcumin and genistein has synergitic activity on antiproliferative effect of human breast cancer cell line (MCF-7).

- Scambia et al. (1994)-quercetin elevates the activity of Adiramycin in multi-drug resistant breast cancer using MCF-7 cell line.

LITERATURE REVIEW

Tabernaemontana divaricata

- Chaiyana et al. (2013)- isolated 3'-R/S-hydroxyvoacamine, a potent acetylcholinesterase inhibitor from the stem of Tabernaemontana divaricata. The alkaloid acted as non- competitive inhibitor of AChE and has IC50 value of 7.00 ± 1.99μM.

- Bao et al. (2013)- isolated five novel vobasinyl-ibogan-type bisindole alkaloids.

- named as tabernaricatines A-E. They have extracted 24 known indole alkaloids, among them; conophylline gave significant anticancer activities with IC50 values of 0.17, 0.35, 0.21, 1.02, and 1.49ȝM on HL-60, SMMC-7721, A- 549, MCF-7, and SW480 cell lines respectively.

- Mukhram et al. (2012)- established the anti-fertility property of Tabernaemontana divaricata flower extracts in rats.

- The extracts were obtained using methanol and water. The anti-fertility effects were studied using estrogenic activity, anti-implantation and early abortifacient effect.

- methanolic extract of Tabernaemontana divaricata at at 500mƥ kg-1, has estrogenic, anti-implantation and abortifacient activity.

- Raj and Balasubramaniam (2011)- studied the antimicrobial properties of Tabernaemontana divaricata.

- The extracts were obtained using petroleum ether, chloroform, methanol and water. Tested against gram positive and negative bacteria

- Had moderate activity on both the bacteria.

- Kam et al. (2004) have isolated five new indole alkaloids namely (3S)-3-cyanocoronaridine,(3S)-3- cyanoisovoacangine, conolobine A, conolobine B, conolidine, and (3R/3S)-3-ethoxyvoacangine.

- Keimei et al. (1998)- isolated conophylline from Tabernaemontana divaricata.

- Arambewela and Ranatunge (1991)- isolated eleven indole alkaloids namely voacangine, voacristine, isovoacristine, coronaridine, isovoacangine, vobasine, voacangine, tabernaemontanine, 19-epi-voacangine from the leaves of Tabernaemontana divaricata.

illustration not visible in this excerpt

OBJECTIVES AND PLAN OF WORK

OBJECTIVES

- Breast cancer is the most prevalent cancer in women. Currently the drugs available for breast cancer have a disadvantage of having severe adverse effects and decreasing the quality of life.
- Guided by the literature review and followed by docking studies of phytoconstituents it was found worthy to scientifically explore Tabernaemontana divaricata w.r.t its phytochemical presence and anticancer activities.
- In the present study, the main aim was to identify the most potent extract against breast cancer from leaves of Tabernaemontana divaricata (L.) R. Br. ex Roem. & Schult.
- From the most potent extract, we aim to isolate the phytoconstituents and to test their efficacy against breast cancer.
- Further docking studies need to be performed, to know the docking poses of known phytoconstituents.
- Antioxidant studies and toxicity studies need to be performed to assess the pharmacological activities of plant extract and isolated compounds.

[...]

Excerpt out of 69 pages

Details

Title
Studies on Anticancer Agents from Natural Sources. The Tabernaemontana Divaricata (L.) R. Br. ex Roem. & Schult.
Course
M. Pharm.
Grade
1
Authors
Year
2014
Pages
69
Catalog Number
V303968
ISBN (eBook)
9783668047570
ISBN (Book)
9783668047587
File size
2825 KB
Language
English
Keywords
Anticancer, Plants, Natural products, Folklore knowledge, Phytochemical, Tabernaemontana divaricata
Quote paper
Dr. Manik Ghosh (Author)Mavuduru Siva Ganesh (Author), 2014, Studies on Anticancer Agents from Natural Sources. The Tabernaemontana Divaricata (L.) R. Br. ex Roem. & Schult., Munich, GRIN Verlag, https://www.grin.com/document/303968

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