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

Abstract, 2014

69 Pages, Grade: 1











- 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

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Prevalence of different types of cancer worldwide, 2012

(Source: World Cancer Research Fund International,


- 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


- 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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- 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


Reproduced from: 9


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- 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.


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.

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- 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.


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Studies on Anticancer Agents from Natural Sources. The Tabernaemontana Divaricata (L.) R. Br. ex Roem. & Schult.
M. Pharm.
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Anticancer, Plants, Natural products, Folklore knowledge, Phytochemical, Tabernaemontana divaricata
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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,


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