The role of pharmacology in anticancer drug development

Peters, Godefridus J.; Govaerts, André; Hendriks, H.R.; Pharmacology, for Eortc

doi:10.5599/admet.6.1.496

Cited by 1 publication

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemotherapy is one of the most reliable methods of treating cancers. While it is desired that low doses of drugs should eliminate the cancer cells, the inability of those drugs to differentiate between the normal and cancerous cells posed a far bigger concern [48]. These side effects make it difficult to rely only on the anticancer activity of drugs, but also their ability to select their target amongst the conglomerates of body cells.…”

Section: Brine Shrimps Lethality Assaymentioning

confidence: 99%

“…These side effects make it difficult to rely only on the anticancer activity of drugs, but also their ability to select their target amongst the conglomerates of body cells. High selectivity with low activity is therefore preferred to the otherwise, in cancer drug development and this depicts high therapeutic value [48]. Throughout the experimental studies, EGS displayed selective activities and has specifically proved to be a potential anticancer drug with a high therapeutic index (high activity and high selectivity).…”

Section: Brine Shrimps Lethality Assaymentioning

confidence: 99%

See 1 more Smart Citation

Anticancer and Apoptotic Potentials of Gliricidia sepium Leaf Extract on Breast HCC1395, Prostate DU145 and Colorectal CT26 Cell Lines

Muhammed

Nakalembe

Olila

et al. 2021

JCTI

View full text Add to dashboard Cite

Background: Plants have become a household name in the quest for effective and safe cancer chemotherapy in the Pharmaceutical industry. We studied the Brine shrimps lethality, antiproliferative and apoptotic potentials of Gliricidia sepium leaf extract against some selected cancer cell lines. Methodology: Plant leaves extraction was done with 70% ethanol and petroleum ether. Twenty four hours old shrimp’s larvae exposure to different concentrations (1 mg/ mL, 100 µg/ mL, 10 µg/ mL and 1 µg/ mL) of the extracts were used to evaluate the cytotoxicity in Brine shrimps lethality assay (BSLA). Three cancer cell lines: Breast (HCC1395); Prostate (DU145); Colorectal (CT26) and one normal cell line (Vero E6) were used for the in-vitro cytotoxicity testing using MTT assay. IC50, CC50 and Selectivity Index (SI) were determined respectively, using standard methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out on HCC1395 and DU145 cell lines. Primers for the genes p53 and BAX were generated and amplified for apoptotic evaluation. The fold change relative to GADPH, the housekeeping gene, was calculated using double delta Ct analysis [2ˉΔΔCT]. Results: The results of BSLA showed that both extracts of G. sepium are strongly toxic (LC50 < 100 µg/ml). However, petroleum ether extract (PGS) exhibited the highest toxicity to the shrimps, with LC50 of 11.95 µg/ml. This is about 8 times more cytotoxic than cyclophosphamide (LC50 of 98.76 µg/ml). On cancer cells, PGS exhibited varying antiproliferative activities; it was high on prostate (IC50 = 12.76 µg/ml), antiproliferative (IC50 = 23.55 µg/ml) and moderately antiproliferative (IC50 = 77.58 µg/ml) on breast and colorectal cancer respectively. PGS CC50 value was greater than 100 µg/ml. Ethanol extract (EGS) showed very high toxicity to all the tested cancer cells (IC50 <20µg/ml) with low cytotoxicity (CC50 = 41.81 µg/ml) to the normal cells. It exhibited a significant difference and high selectivity index across all the cell lines used in this study. EGS also upregulated both p53 and BAX biomarkers in the qRT-PCR apoptotic study. Conclusion: The leaf extracts of G. sepium is a potential anticancer agent. The 70% ethanol extract selectively induced antiproliferative activities on cancer cells and upregulated apoptotic genes. The Petroleum ether extract also showed very low cytotoxicity to the normal cells. The plant should be considered a novel candidate for further studies.

show abstract

Section: Brine Shrimps Lethality Assaymentioning

confidence: 99%

Section: Brine Shrimps Lethality Assaymentioning

confidence: 99%