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Biol 3290 > Pages 16-20 - Cancer Treatments > Flashcards

Pages 16-20 - Cancer Treatments Flashcards

1
Q

What were the sources of anti- cancer drugs?

A

Naturally occurring secondary products from plants

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2
Q

How many anti- cancer drugs do we have today ?

A

77

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3
Q

Provide a breakdown of 77 anti - cancer drugs

A

12- proteins
30- secondary products or their semi synthetic derivatives from higher plants
18- synthetics to mimic 2nd producys
17- total synthetics

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4
Q

How were many anti- cancer drugs developed?

A

Random screening of plant material
Modification (semi synthesis) of 2nd products

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5
Q

Drugs used in cancer chemotherapy are …..

A

Cytotoxic

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6
Q

What is cytotoxic ?

A

Main component cancer chemotherapy - kill specific cell
Kill cancerous cells
prevention from dividing and poliferating

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7
Q

Cytotoxin is used in ?

A

Chemotherapy
Therapeutically after semi synthetic synthesis to make them safer and effective

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8
Q

However what can cause limit use of cytotoxin?

A

Adverse side affects

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9
Q

List the anti- cancer drugs derived from plants

A

Rosy periwinkle
Pacific yew
Mayapple / american mandrake
Tree of joy
Petty spurge
Dysoxylum
Plum yew
Maytennus

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10
Q

Define Rosy Periwinkle

A

Small annual plant growing to a 1m
Native to madagascar
Common horticulture plant
Has become serious invasive weed in some cultures

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11
Q

What were some old uses of Rosy periwinkle?

A

Anti diabetic in Madagascar and Carribean (periwinkle tea cheap subs to insulin)
Smith Africa , Phillipes, southern europe - orally to lower blood sugar
South africa - diabetes and rheumatism
Brazilians - hemorrhage and scurvy

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12
Q

Tests on Rosy Periwinkle

A

NCI tested for anti- cancer properties - none
Noble and charles for diabetic properties - none found

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13
Q

If none of the tests were successful, how did rosy periwinkle become and imp anti - cancer drug?

A

Noble and charles tested for anti- diabetes- no success
Found out
- extract caused dec in WBC
- reduced bone marrow activity
- the affect on WBC led to investigation against treating leukaemia cancer

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14
Q

Leukemia cancer

A

Fatal blood disorder - abnormal increase in cancerous WBC

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15
Q

What are the two anti- cancer components found in rosy periwinkle?

A

Vinca Alkaloid - vinblastine and vincristine

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16
Q

Semi synthetic of vinca alkaloid

A

Vinorelbin

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17
Q

Which cancers did vinblastine treat

A

Hodgkin disease
Choriocarcinoma
Neoplasms

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18
Q

Hodgkin diseases

A

Cancer on lymphatic system

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19
Q

Choriocarcinoma

A

Cancer on placenta

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20
Q

Neoplasm

A

Abnormal tissue growths - tumors

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21
Q

Whats cancer did vincristine treat

A

Acute childhood leukemia

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22
Q

What cancers vinorelbine treated

A

Breast cancer
Non- small cell lung cancer

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23
Q

How do vinca alkaloids work?

A

Interfere with the spindle fibre formation during mitosis
Most effective when taken in comb with other drugs

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24
Q

PACIFIC YEW

A

Small , slow growing carniferous tree
Native to coast and intermountain regions of W.N America
Uncommon tree occurring as isolated indv in forest understory
Height of 15m
Diameter of 60cm

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25
Q

What were some old uses

A

W.N American indg people - stomach aches
Tsimshian of coastal British columbia - anti - cancer

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26
Q

When was the cytotoxin in pacific yew first discovered?

A

Us agriculture department and NCI testing anti- cancer properties in random plant sps across the world, and cytotoxin was discovered during this time . Therefore, ethnobotanical info had no value (mid 20th century)

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27
Q

What did the NCI do after ‘ many years ‘ discovering cytotoxin in pacific yew?

A

Compiled list of anti-cancer drugs , based on info from historical manuscripts - bowers manuscripts

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28
Q

Which historical manuscript did the NCI take the anti- cancer cytotoxin drug info from?

A

Bowers manuscript

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29
Q

Bowers manuscripts

A

4-6th century Sanskrit of Indian medicine mentioning the use of yew as anti- cancer drug in both Ayurvedic and Chinese medicine

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30
Q

Which part of pacific yew had the cytotoxin?

A

Bark extracts had strong cytotoxin effect in their in vitro system

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31
Q

What was the principal component in the bark extract

A

Alkaloid - taxol (renamed - paclitaxel)

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32
Q

Paclitaxel was used to treat which cancers ?

A

Ovarian and breast cancer

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33
Q

What was the consequences in use of paclitexel?

A

Required in very high doses
15- 20kg of paclitaxel - ovarian
200- 300 kg to treat other additional cancers
Total pacific yew - 1500 tons
Lead to extinction

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34
Q

Resolution to the soon extinctions of pacific yew due to large doses ?

A

Semi synthetic of paclitaxel using BECCATIN III as a precurosr.
Obtained from leave sand small branches of European yew
Which is comparatively fast growing

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35
Q

Define European yew

A

Comparatively large and fast growing m and common hedegrow sps in europe

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36
Q

What is the most common source of commercial paclitaxel

A

Hedgerow clippings from European yew

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37
Q

Mayapple / american mandrake

A

Long lived understory harbaceous
60m tall
Native to eastern decisions forest of north america
First species in spring , produces umbrella shaped , deeply lobed leave from rhizome

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38
Q

What is the special about mayapple /american mandrake.

A

First sps in spring
Produce umbrella shaped, deeply lobed leaves from rhizomes

39
Q

Which part is used medicinally in mayapple?

A

Umbrella shaped, deep lobed leaves from rhizome

40
Q

What are the old uses of mayapple? Lost the new uses as well

A

Cherokee, Delaware, and Iroquois, American colonist - powerful laxative
150 yrs mayapple raisin listed as an effective laxative in the American pharmacopoeia
Treatment of veneral warts,
Treatment of cancerous tumors and polyps

New uses
- anti- viral
-topical treatment for genital warts
- not as an anti- cancer drug due to high toxicity side affects

41
Q

What is the principal component in raisin

A

Lignan- podophyllotoxin

42
Q

Podophyllotoxic is effective against which type of cancers ?

A

Kill Some types of cancers cells
Damages Tumours

43
Q

Why was podophyllotoxin discontinued

A

Toxic side affects as an anti - cancer drug

44
Q

How was the toxic side affect resolved

A

Formation of semi- synthetic of safer ,more effective drugs

45
Q

What were the semi- synthetics of podophyllotoxins?

A

Teniposides
Etoside

46
Q

Teniposide treats which cancers?

A

Childhood leukemia

47
Q

Etoposides treats

A

Leukaemia , lymphomas, brain and bladder tumors

48
Q

How does the podophyllotoxin works?

A

Anti-mitotic drug
Bind to tubulin
Prevents microtuble formation during cell division

49
Q

How do teniposides and etoposides works?

A

Inhibition of topoisomerase I,
Enzyme that is essential for the maintenance of DNA

50
Q

Tree of Joy

A

Small, fast growing, deciduous tree native to southern china and Tibet .

51
Q

Tree of joy is also called

A

Xi - chu

52
Q

Used esp in which medicine?

A

Chinese medicine

53
Q

Which part of the tree was used in medicine ?

A

Bark, roots, fruits

54
Q

What was trees of joy used for in chinese medicine?

A

Treating carcinomas of
- stomach
- rectum
- colon
- bladdar

55
Q

What is the principal compound in it ?

A

Camptithecin

56
Q

How was camptithecin first identifiied?

A

USDA screening of many plants for cortisone precursor

57
Q

Later on camptothecin was used for treating

A

Gastrointestinal tumors

58
Q

Why was the tree of joy declined even when it was deemed affective in gastrointestinal tumors?

A

Severe side effects

59
Q

Resolution to this was S.S.A of comptothecin was?

A

Semi synthetics of comptothecin

60
Q

Semi synthetics of comptothecin?

A

Topotecan
Irinotecan
Other demi sythetics eg lutotecan, exatecan)

61
Q

Topotecan

A

Ovarian cancer

62
Q

Irinotecan

A

Colorectal canvers

63
Q

Mode of action of topotecan and irinotecan

A

Inhibit action of topoisomerase l like (teniposide and etoposide).

64
Q

Other semi synthetics of camptothecin

A

Chemotherapeutic treatement of leukemia , lymphoma, CNS cancer, breast cancer

65
Q

Camptothecin compounds

A

Potential drug to AIDS - due to antiviral activity of some camptothecin compounds

66
Q

Petty spurge

A

Small, annual, euphorb native to Europe and Westrn asia
Occurs as a weed in Australia and america

67
Q

How was it used in old times

A

Treating skin lesions and cancers esp basal cell carcinomas

68
Q

What is the petty spurge principal component ?

A

Ingenol mebutate

69
Q

What is ingenol mevutate used for now

A

Non melanoma skin cancers esl basal cell carcinomas
Premalognant actinic keratosis

70
Q

Actinin keratosis

A

Development of thick scaly, crusty, patches of skin following sun exposure in fair skinned patients
Pre carcenous , 20 % risk of progressing to aquamous cell carcinoma

71
Q

Mode of action of ingenol mubutate

A

Applied 2-3 days
Induces cell death
Promotes healing and restoring normal histological skin
Targets sub epidermal vasculature
Inflammatory and immunostimulant props

72
Q

Dysolxylum

A

This genus has 60 large trees belong to meliacea family
Mative to indian subcontinent and adj S.E asia and SW. china

73
Q

Used in which medicine

A

Ayurvedic

74
Q

What was this sp used for in ayurvedic medicine?

A

Anti -inflammatory agent
Diuretic and CNS depressant
D. Malabaricum - treats rheumatoid arthritis

75
Q

Whats are the principal component in Dysocoxylum?

A

Chromane alkaloid - Rohitukine from the bark

76
Q

Rohitukine is isolated from what part of which sps?

A

Bark of D binectiferum
2-3 % -7%

77
Q

Over 100 semi synthetic formed one if them is anticancer called?

A

Flavopridol (alvocidib)

78
Q

Falvopridol against which cancers ?

A

Ovarian , breast and lung cancer

79
Q

Mode of action of flavoprodol

A

Inhibitor of cyclin decpendent kinases
Induces cell death
Cell growth inhibitor

80
Q

Falvopridol under development for

A

Treating leukemia
Lymphoma
Esphageal lung and liver cancer

81
Q

Falvopridol is used alone or in com

A
82
Q

Pendent kinases?

A

Enzymes controlles progression of the cell cycle

83
Q

Falvopridol under investigation for

A

Rheumatoid arthritis
Anti- viral agent
Contraceptive disease

84
Q

Falvopridoll granted orphan status is US

A

For treating acute myeloid leukemia.
Orphan status for rare disease

85
Q

PLUM YEW

A

Small, slow growing caniferous tree native to japan and korea

86
Q

When was plum yew noticed ?

A

Us and china found anti cancer properties in the bark of cephalotaxus sp

87
Q

Plum yew extract shoed effects against

A

Leukemi and tumor cells

88
Q

Principal component in plum yew

A

Alkaloid omacetaxin

89
Q

Semi synthetic of amacetaxin

A

Imanitib

90
Q

Imanitib is affective against which cancer

A

Chronic myeloginous leukemia

91
Q

Mode of action of imanitib

A

Inhibts enzyme that is specific to cancer cell

92
Q

Renewed intrest in omacetoxin after imatinib

A

Due to resistance to imatinib

93
Q

Oxmacetaxine approved by us for treatement of

A

Chronic myelogenous leukaemia especially in patients resistant to imatinib

94
Q

Mode of action of omacetaxin

A

Inhibit elongation steps in protein syn

Biol 3290 (7 decks)

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