3. Conclusion

CML is a hematological malignancy that arises due to chromosomal translocation resulting in the presence of Ph chromosome. Initially, TKIs were designed to compete with the ATP binding site of BCR-ABL. TKIs effectively inhibited wild-type BCR-ABL; however, mutations in BCR-ABL and overexpression of drug efflux proteins following treatment decreased their potency.

Since, there is a need for alternative strategy to develop new BCR-ABL inhibitors; NPs (obtaining from living organisms) offers an alternate, effective and inexpensive design for CML therapy. Moreover, they have less (or) no side effects. Studies conducted so far have revealed that many NPs inhibit CML cell proliferation and, in addition, induce cell death through apoptosis. NPs alone or in combination with other TKIs are able to reverse the MDR, thereby increasing the sensitivity of TKIs towards CML. Moreover, many NPs are able to differentiate CML cells into erythroid, monocyte or macrophage lineage. In vivo results have clearly shown that NPs potently suppress tumor growth. In sum, NPs serve as an inexhaustible source which renders an attractive alternate strategy to combat CML.

#### Conflict of interests

The authors declare that they do not have any competing interests.

#### Abbreviations

3. Conclusion

MeOH extract of Rhinella jimi Stevaux (Anura: Bufonidae) skin

22 Anti-cancer Drugs - Nature, Synthesis and Cell

MeOH extract of Hypericum perforatum L.flower extract

HEX, DCM, EtoAc, butanol and MeOH extracts of Helichrysum zivojinii Černjavski and Soška

Acetate: MeOH (95:5), acetate, chloroform and HEX fractions of Erythroxylum caatingae plowman

Polyphenolic extract of Ichnocarpus

Coptis chinensis and Epimedium

Sangre de Drago is red viscous latex extract of Croton lechleri

Crude MeOH extracts of Luehea candicans Mart. et Zucc. branches

Ponicidin (Rabdosia rubescens

Scutellaria litwinowii Bornm. and

Viscin, (lipophilic extract from

Table 8. Anti-CML activity of plant extracts.

fructescens leaves

sagittatum extracts

and leaves

extract)

Sint. ex Bornm.

Viscum album L)

CML is a hematological malignancy that arises due to chromosomal translocation resulting in the presence of Ph chromosome. Initially, TKIs were designed to compete with the ATP binding site

AQE, aqueous, DCM, dichloromethane, HEX, hexane, EtOH, ethanol, EtoAc, ethyl acetate, MeOH, methanol, ^TGI,

Plant extract IC50 value on K562 cells Mechanism of action References

11.78 ± 0.94, 23.82 ± 6.54, 27.52 ± 4.96, 50.37 ± 3.28 and 74.88 ± 7.57 μg/ml (for 72 h)

13.1 ± 0.63, 9.86 ± 0.56, 11.21 ± 0.46, 33.58 ± 1.33 μg/ml

DCM extract of Arctium lappa root ^17 μg/ml – [264] Alisma orientalis (Sam) Juzep extract – Reverse of MDR [265]

EtOH extract of Orbignya speciosa 33.9 ± 4.3 μg/ml – [267]

Dionysia termeana extract 20 μg/ml – [270] Ganoderma lucidum extract \*50 μg/ml – [271]

Nerium oleander extract – ↓p-gp [274]

Swietenia mahagoni leaf extract – ↟ caspases 3,9, Cyt. C release and

tumor growth inhibition,\*ED50, –effective concentration; # GI50, growth inhibition.

\*235 μg/ml – [260]

– Induced apoptosis [261]

– At 5, 10, 20 μg/ml con. ↓K562 cell

proliferation

29 and74 μg/ml – [268]

2.5 ± 0.3 μg/ml – [269]

#8.1–5.4 μg/ml – [273]

– ↓ Bcl-2 and ↑ Bax, caspase 3 & PARP cleavage

– ↟ caspase 3,8, PARP cleavage, Bax/ Bcl-2 ratio

⊥G2-M phase

252 ± 37 μg/ml – [280]

– [262]

– [263]

[266]

[276]

[278]

[279]


