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University of Horticultural Sciences,
                  Bagalkot
K. R. C. College of Horticulture, Arabhavi




                           By,
                                 Rahul S. Phatak
                                 UHS11PGM140
                                 Dept. of PMA
«dAiÀĪÁtÂ, 12. ¸É¥ÀÖA§gï. 201
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 treatment
Only 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      Mechanism of
                          cancer cells              action
Catharanthus roseus Leukemias, lyphomas          Mitotic block
                    and lung cancer
Berberineeris sp.   Breast, prostrate and          Apoptosis
                    lung cancer
Gloriosa superba       Leukemia                   Anti-mitotic
Curcuma longa          Colon and pancreatic        Unknown
                       cancer
Zingiber officinalis   Breast and lung cancer      Un known
Andrographis           Colon cancer                Apoptosis
paniculata

                                           (Nirmala et al., 2011)
Table 1Contd.
Palargonium          Breast cancer                Un known
graveolens
Boesenbergia         Breast and colon cancer    Apoptosis and
pandurata                                      cell cycle arrest
Ruta graveolens      Colon & prostate cancer   Cell cycle arrest
Ocimum sanctum       Lung cancer                 Inhibition of
                                                   invasion
Magnolia             Prostate cancer             Not known
officinalis
Achyranthes          Pancreatic cancer            Apoptosis
aspera
Solanum nigrum       colon and breast cancer      Apoptosis
Artemisia vulgaris   Prostate & colon cancer      Apoptosis
                                          (Nirmala et al., 2011)
 Solanum nigrum
  Black nightshade
  Solanaceae
  Berries
  Antipyretic and Diuretic



 Artemisia vulgaris
  Asteraceae
  Whole herb
  Intestinal worms, Asthma,
  Sterility
*p < 0.05, and **p < 0.01

Figure 1: Effect of aqueous extracts of Artemisia vulgaris on
                 clonoginicity of cancer cells
                                               (Nawab et al., 2011)
**p < 0.01
    Figure 2: Effect of aqueous extracts of Solanum nigrum on
                   clonoginicity of cancer cells
                                                (Nawab et al., 2011)
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

Fraction A - with 1:1 methanol/water
Fraction B -with 100% methanol
                                                     (Kirana et al., 2007)
Figure 3: different cell cycle check points by plant constituents
Figure 4: Effect of Panduratin A on cell cycle
                                         (Kirana et al., 2007)
Figure 5: Total apoptosis in HT-29 cancer cells after 48 h
treatment with different concentrations of Panduratin A.


                                                (Kirana et al., 2007)
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)
p53     Tubulin      Merge




         Control
         50µg/ml
         100µg/ml




Plate 2: Effect of R. graveolens extract treatment on induction of p53
                        protein in cancer cells

                                                         (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 tumours
A. 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
** P < 0.01
   Figure 12: Effect of EEOS on the formation of tumour
              nodules in LLC-inoculated mice.

                                                (Kim et al., 2010)
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




WA, 10-60 indicate drug doses in mg/kg
a determined at one week of treatment
b, c significant compared to control (b P < 0.05,c P < 0.01)
                                                               (Devi et al., 1995)
• 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)
* P < 0.05, ** P < 0.01




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)
Conclusion


       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
T

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Tropical Anticancerous plants

  • 1.
  • 2. University of Horticultural Sciences, Bagalkot K. R. C. College of Horticulture, Arabhavi By, Rahul S. Phatak UHS11PGM140 Dept. of PMA
  • 4.
  • 5. Cancer is generally considered to comprise more than 100 diseases, each characterized by uncontrolled growth and spread of abnormal cells. (Watson, 2006)
  • 6.
  • 7. Causes  Internal factors Inherited mutation, hormones, immune condition and mutation that occur from metabolism.  External factors Tobacco, Chemicals, Radiation and Infectious organisms (Baudino, 2004)
  • 8.
  • 9. Genes Cancer
  • 10.
  • 11. 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)
  • 12. 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)
  • 13. How to cure..? Surgery Oldest known treatment Only if cancer has not metastasized
  • 14. Radiation • Radiotherapy • By focusing high-energy rays on cancer cells • May cause side effects
  • 15. Chemotherapy Toxic drugs are needed Focus is to trigger the apoptotic programme Inhibition, blocking effect, anti progression Natural, synthetic or both
  • 16.
  • 17. Table 1: Some anti-cancerous plants used in cancer therapy Plant species Experiments on various Mechanism of cancer cells action Catharanthus roseus Leukemias, lyphomas Mitotic block and lung cancer Berberineeris sp. Breast, prostrate and Apoptosis lung cancer Gloriosa superba Leukemia Anti-mitotic Curcuma longa Colon and pancreatic Unknown cancer Zingiber officinalis Breast and lung cancer Un known Andrographis Colon cancer Apoptosis paniculata (Nirmala et al., 2011)
  • 18. Table 1Contd. Palargonium Breast cancer Un known graveolens Boesenbergia Breast and colon cancer Apoptosis and pandurata cell cycle arrest Ruta graveolens Colon & prostate cancer Cell cycle arrest Ocimum sanctum Lung cancer Inhibition of invasion Magnolia Prostate cancer Not known officinalis Achyranthes Pancreatic cancer Apoptosis aspera Solanum nigrum colon and breast cancer Apoptosis Artemisia vulgaris Prostate & colon cancer Apoptosis (Nirmala et al., 2011)
  • 19.  Solanum nigrum Black nightshade Solanaceae Berries Antipyretic and Diuretic  Artemisia vulgaris Asteraceae Whole herb Intestinal worms, Asthma, Sterility
  • 20. *p < 0.05, and **p < 0.01 Figure 1: Effect of aqueous extracts of Artemisia vulgaris on clonoginicity of cancer cells (Nawab et al., 2011)
  • 21. **p < 0.01 Figure 2: Effect of aqueous extracts of Solanum nigrum on clonoginicity of cancer cells (Nawab et al., 2011)
  • 22. Plate 1: Effect of aqueous extracts on induction of apoptosis in various cancer cells (DNA fragmentation assay). (Nawab et al., 2011)
  • 23. Boesenbergia pandurata (Kaempferia pandurata) Zingiberaceae Panduratin A Traditionally used as general tonic
  • 24. Figure 3: Influence of plant extracts on HT-29 colon cancer cells Fraction A - with 1:1 methanol/water Fraction B -with 100% methanol (Kirana et al., 2007)
  • 25. Figure 3: different cell cycle check points by plant constituents
  • 26. Figure 4: Effect of Panduratin A on cell cycle (Kirana et al., 2007)
  • 27. Figure 5: Total apoptosis in HT-29 cancer cells after 48 h treatment with different concentrations of Panduratin A. (Kirana et al., 2007)
  • 28. Figure 6: Effect of diets on body weight of rats (Kirana et al., 2007)
  • 29.  Ruta graveolens (Garden rue) Rutaceae used as an abortifacient, insect repellant, treatment for arthritis and ulcers
  • 30. Figure 7: Effect of varying concentrations of R. graveolens extract on clonogenicity of HCT116 , RKO and DU-145 cancer cells (Fadlalla, 2011)
  • 31. p53 Tubulin Merge Control 50µg/ml 100µg/ml Plate 2: Effect of R. graveolens extract treatment on induction of p53 protein in cancer cells (Fadlalla, 2011)
  • 32. Plate 3: Effect of R. graveolens extract treatment on membrane bleb formation. (Phase-contrast micrography of treated cells) (Fadlalla, 2011)
  • 33. Figure 8: Caspase-3 activation assay (Caspase activity kinetics was recorded as absorbance at 405 nm.) (Fadlalla, 2011)
  • 34. • Achyranthes aspera Amaranthaceae
  • 36. Plate 4: Luciferase expressing tumours A. day 4 (baseline) of treatment demonstrate the tumour establishment B. day 33 captures the effect of treatment. (Subbarayan et al., 2012)
  • 37. Figure 9: Effect of Achyranthes aspera leaf extract treatment on weight of tumour (Subbarayan et al., 2012)
  • 38. Figure 10: Expression profile of selected genes in tumour tissues from control and treated mice. (Subbarayan et al., 2012)
  • 39. Plate 5: IHC results of cleaved caspase-3 and pAkt in human pancreatic tumour grown subcutaneously in athymic mice. (Subbarayan et al., 2012)
  • 40. • Curcuma longa Zingiberaceae Curcumin
  • 41. Figure 11: Dose response of docetaxel and curcumin against A549 lung cancer cells. (Yin et al., 2011)
  • 42. 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)
  • 43. Plate 6: Excised tumours of subcutaneous A549 lung cancer xenograft bearing nude mice after 15 days of single dose therapy (Yin et al., 2011)
  • 44. • Ocimum sanctum Holy basil Lamiaceae anti-inflammatory anti-ulcer anti-carcinogenic
  • 45. ** P < 0.01 Figure 12: Effect of EEOS on the formation of tumour nodules in LLC-inoculated mice. (Kim et al., 2010)
  • 46. Plate 7: Effect of EEOS on the formation of tumour nodules in LLC-inoculated mice. (Kim et al., 2010)
  • 47. Plate 8: Effect of EEOS on activation of MMP-2 and -9 (Zymographic assay) (Kim et al., 2010)
  • 48. • Withania somnifera Solanaceae Withanin, Withaferin General tonic, sexual disorders
  • 49. Table 3: Effect of withaferin A on mice bearing Ehrlich ascites carcinoma WA, 10-60 indicate drug doses in mg/kg a determined at one week of treatment b, c significant compared to control (b P < 0.05,c P < 0.01) (Devi et al., 1995)
  • 50. • Magnolia officinalis Magnoliaceae Magnolol used to treat acute pain, cough and gastrointestinal disorders
  • 51. Figure 13: Effect of Magnolol on PC-3 Human Prostate Carcinoma cell proliferation (MTT assay) (Hwang and Park, 2010)
  • 52. * P < 0.05, ** P < 0.01 Figure 14: Effect of Magnolol on PC-3 Human Prostate Carcinoma cell invasion (Hwang and Park, 2010)
  • 53. * P < 0.05, ** P < 0.01 Figure 15: Effect of Magnolol on MMP expression (Hwang and Park, 2010)
  • 54. Conclusion 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
  • 55. T