Seminar-I

Tropical anticancerous plants

By, Rahul S. Phatak UHS11PGM140 Dept. of PMA

University of Horticultural Sciences, BagalkotK. R. C. College of Horticulture, Arabhavi

«dAiÀĪÁtÂ, 12. ¸É¥ÀÖA§gï. 2012

Cancer is generally considered to comprise more

than 100 diseases, each characterized by uncontrolled

growth and spread of abnormal cells.

(Watson,

2006)

Causes

Internal factors

Inherited mutation, hormones, immune condition and mutation that occur from metabolism.

External factors

Tobacco, Chemicals, Radiation and Infectious organisms

(Baudino, 2004)

Genes Cancer

Types of cancer

There are Four types according to body tissue from

which they arise

1. Carcinoma : epithelial cells lining lung, liver, breast,

prostate and pancreas

2. Sarcoma: muscles, nerves and bones

3. Lymphoma: cells in lymph glands

4. Leukemia: blood forming tissue

(Bagchi and Preuss, 2005)

Cancer globally…

• Every year, diagnosed in 10 million people and account

for 7.1 million deaths (12.5 % of global total)

• Second to cardiovascular diseases

• Global cancer rates could increase by 50% to 15 million

by 2020

• Due to smoking and adoption of unhealthy lifestyles

• Brest cancer, colon cancer, prostate cancer, lung cancer

and blood cancer are found major.(WHO, 2009)

How to cure..?

Surgery Oldest known treatmentOnly if cancer has not metastasized

Radiation• Radiotherapy• By focusing high-energy rays on cancer cells• May cause side effects

Chemotherapy

Toxic drugs are needed

Focus is to trigger the apoptotic programme

Inhibition, blocking effect, anti progression

Natural, synthetic or both

Table 1: Some anti-cancerous plants used in cancer therapy

Plant species Experiments on various cancer cells

Mechanism of action

Catharanthus roseus Leukemias, lyphomas and lung cancer

Mitotic block

Berberineeris sp. Breast, prostrate and lung cancer

Apoptosis

Gloriosa superba Leukemia Anti-mitotic

Curcuma longa Colon and pancreatic cancer

Unknown

Zingiber officinalis Breast and lung cancer Un known

Andrographis paniculata

Colon cancer Apoptosis

(Nirmala et al., 2011)

Palargonium graveolens

Breast cancer Un known

Boesenbergia pandurata

Breast and colon cancer Apoptosis and cell cycle arrest

Ruta graveolens Colon & prostate cancer Cell cycle arrest

Ocimum sanctum Lung cancer Inhibition of invasion

Magnolia officinalis

Prostate cancer Not known

Achyranthes aspera

Pancreatic cancer Apoptosis

Solanum nigrum colon and breast cancer Apoptosis

Artemisia vulgaris Prostate & colon cancer Apoptosis

(Nirmala et al., 2011)

Table 1Contd.

Solanum nigrum

Black nightshade

Solanaceae

Berries

Antipyretic and Diuretic

Artemisia vulgaris

Asteraceae

Whole herb

Intestinal worms, Asthma, Sterility

Figure 1: Effect of aqueous extracts of Artemisia vulgaris on clonoginicity of cancer cells

(Nawab et al., 2011)

*p < 0.05, and **p < 0.01

In-vitro

Figure 2: Effect of aqueous extracts of Solanum nigrum on clonoginicity of cancer cells

(Nawab et al., 2011)

**p < 0.01

In-vitro

Plate 1: Effect of aqueous extracts on induction of apoptosis in various cancer cells (DNA fragmentation assay).

(Nawab et al., 2011)

Boesenbergia pandurata (Kaempferia pandurata)

Zingiberaceae

Panduratin A

Traditionally used as general tonic

Figure 3: Influence of plant extracts on HT-29 colon cancer cells

(Kirana et al., 2007)

Fraction A - with 1:1 methanol/water Fraction B -with 100% methanol

In-vitro

Figure 3: different cell cycle check points by plant constituents

Figure 4: Effect of Panduratin A on cell cycle

(Kirana et al., 2007)

In-vitro

Figure 5: Total apoptosis in HT-29 cancer cells after 48 h treatment with different concentrations of Panduratin A.

(Kirana et al., 2007)

In-vitro

Figure 6: Effect of diets on body weight of rats

(Kirana et al., 2007)

Ruta graveolens (Garden rue)

Rutaceae

used as an abortifacient, insect repellant, treatment for arthritis and ulcers

Figure 7: Effect of varying concentrations of R. graveolens extract on clonogenicity of HCT116 , RKO and DU-145 cancer cells

(Fadlalla, 2011)

In-vitro

Plate 2: Effect of R. graveolens extract treatment on induction of p53

protein in cancer cells

Con

trol

50µ

g/m

l10

0µg/

ml

p53 Tubulin Merge

(Fadlalla, 2011)

Plate 3: Effect of R. graveolens extract treatment on membrane bleb formation. (Phase-contrast micrography of treated cells)

(Fadlalla, 2011)

Figure 8: Caspase-3 activation assay (Caspase activity kinetics was recorded as absorbance at 405 nm.)

(Fadlalla, 2011)

• Achyranthes aspera

Amaranthaceae

(Subbarayan et al., 2012)

Plate 4: Luciferase expressing tumoursA. day 4 (baseline) of treatment demonstrate the tumour establishment

B. day 33 captures the effect of treatment.

(Subbarayan et al., 2012)

Figure 9: Effect of Achyranthes aspera leaf extract treatment on weight of tumour

(Subbarayan et al., 2012)

Figure 10: Expression profile of selected genes in tumour tissues from control and treated mice.

(Subbarayan et al., 2012)

Plate 5: IHC results of cleaved caspase-3 and pAkt in human pancreatic tumour grown subcutaneously in athymic mice.

(Subbarayan et al., 2012)

• Curcuma longa

Zingiberaceae

Curcumin

Figure 11: Dose response of docetaxel and curcumin against A549 lung cancer cells.

(Yin et al., 2011)

Table 2: Effect of Docetaxel and Curcumin against tumour growth of A549 xenografts

* P < 0.05 vs, the group of docetaxel

(Yin et al., 2011)

Plate 6: Excised tumours of subcutaneous A549 lung cancer xenograft bearing nude mice after 15 days of single dose

therapy

(Yin et al., 2011)

• Ocimum sanctum

Holy basil

Lamiaceae

anti-inflammatory

anti-ulcer

anti-carcinogenic

Figure 12: Effect of EEOS on the formation of tumour nodules in LLC-inoculated mice.

(Kim et al., 2010)

** P < 0.01

Plate 7: Effect of EEOS on the formation of tumour nodules in LLC-inoculated mice.

(Kim et al., 2010)

Plate 8: Effect of EEOS on activation of MMP-2 and -9 (Zymographic assay)

(Kim et al., 2010)

• Withania somnifera

Solanaceae

Withanin, Withaferin

General tonic, sexual

disorders

Table 3: Effect of withaferin A on mice bearing Ehrlich ascites carcinoma

(Devi et al., 1995)

WA, 10-60 indicate drug doses in mg/kga determined at one week of treatmentb, c significant compared to control (b P < 0.05,c P < 0.01)

• Magnolia officinalis

Magnoliaceae

Magnolol

used to treat acute pain,

cough and

gastrointestinal disorders

Figure 13: Effect of Magnolol on PC-3 Human Prostate Carcinoma cell proliferation (MTT assay)

(Hwang and Park, 2010)

In-vitro

Figure 14: Effect of Magnolol on PC-3 Human Prostate Carcinoma cell invasion

(Hwang and Park, 2010)

* P < 0.05, ** P < 0.01

Figure 15: Effect of Magnolol on MMP expression(Hwang and Park, 2010)

* P < 0.05, ** P < 0.01

Anticancer compounds from many plants have been found significantly active against various cancer cells in animal models.

Further research on precise molecular mechanisms and targets for cell growth inhibition may lead to better treatment of cancer

Conclusion

Tobacco causes cancer; cancer kills.

Thank you…