Most of the classical drugs used today to destroy cancer cells lead to the development of acquired resistance in those cells by limiting cellular entry of the drugs or exporting them out by efflux pumps. As a result, higher doses of drugs are usually required to kill the cancer cells affecting normal cells and causing numerous side effects. Accumulation of the therapeutic level of drugs inside the cancer cells is thus required for an adequate period of time to get drugs' complete therapeutic efficacy minimizing the side effects on normal cells. In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in this study to make complexes with three classical anticancer drugs, methotrexate, cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to apatite were evaluated by absorbance and HPLC analysis and the therapeutic efficacy of drug-apatite complexes was determined by cell viability assay. Carbonate apatite demonstrated significant binding affinity towards methotrexate and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7 and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite with resulting tiny particles less than 100 nm in diameter further promoted binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted apatite nanoparticles have the high potential for loading substantial amount of anti-cancer drugs with eventual more therapeutic effectiveness.

Clausenidin is a pyranocoumarin majorly found in medicinal herbs of the Rutaceae family used to treat cancer patients locally in Asia. The compound is presumed to have anti-cancer cell effect but its exact mechanism of action is still unknown. The study aimed to evaluate the effect of pure clausenidin on p53-mediated apoptosis as well as other cell death pathways in colon cancer (HT-29) cell lines. The antiproliferative effect of clausenidin by cell cycle and annexin V assay using flow cytometry was evaluated. Morphological analysis of the treated cells was performed using scanning and transmission electron microscopy. Furthermore, the effect of p53 mRNA on cell cycle and apoptosis-related genes and proteins in clausenidin-treated HT-29 cells was investigated using qPCR and Western blot assays, respectively. Clausenidin induced a p53 dependent G0/G1 cell cycle arrest in HT-29 cells. It was also observed that the anti-cancer cell effect of clausenidin occurred via p53 mediated activation of p21, bax and transrepression of survivin and bcl 2 that culminated in the apoptosis of colon cancer cells. The transmission electron microscopy (TEM) micrographs confirmed the occurrence of apoptosis in clausenidin-treated HT-29 cells. Clausenidin is a potent anti-HT-29 cell agent that can be used to treat colon tumors.